Skip to main content
NCBI home page
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2021 Jul 30;64(12):2030–2044. doi: 10.1007/s11427-021-1961-1

Understanding the “SMART” features of hematopoietic stem cells and beyond

Shiru Yuan 1, Guohuan Sun 1, Yawen Zhang 1, Fang Dong 1,2,3, Hui Cheng 1,2,3,✉, Tao Cheng 1,2,3,✉
PMCID: PMC8328818  PMID: 34341896

Abstract

Since the huge success of bone marrow transplantation technology in clinical practice, hematopoietic stem cells (HSCs) have become the gold standard for defining the properties of adult stem cells (ASCs). Here, we describe the “self-renewal, multi-lineage differentiation, apoptosis, rest, and trafficking” or “SMART” model, which has been developed based on data derived from studies of HSCs as the most well-characterized stem cell type. Given the potential therapeutic applications of ASCs, we delineate the key characteristics of HSCs using this model and speculate on the physiological relevance of stem cells identified in other tissues. Great strides are being made in understanding the biology of ASCs, and efforts are now underway to develop safe and effective ASC-based therapies in this emerging area.

Keywords: stem cell biology, adult stem cells, hematopoietic stem cells

Acknowledgements

This work was supported by the Ministry of Science and Technology of China (2016YFA0100600, 2017YFA0103400, 2020YFE0203000), the National Natural Science Foundation of China (81922002, 81730006, 81890990, 81870086, 82070112), the CAMS Initiative for Innovative Medicine (2017-I2M-3-009, 2016-I2M-1-017), and Distinguished Young Scholars of Tianjin (19JCJQJC63400).

Compliance and ethics The author(s) declare that they have no conflict of interest.

Contributor Information

Hui Cheng, Email: chenghui@ihcams.ac.cn.

Tao Cheng, Email: chengtao@ihcams.ac.cn.

References

  1. Adams GB, Chabner KT, Alley IR, Olson DP, Szczepiorkowski Z M, Poznansky MC, Kos CH, Pollak MR, Brown EM, Scadden DT. Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor. Nature. 2006;439:599–603. doi: 10.1038/nature04247. [DOI] [PubMed] [Google Scholar]
  2. Alevra M, Mandad S, Ischebeck T, Urlaub H, Rizzoli SO, Fornasiero EF. A mass spectrometry workflow for measuring protein turnover rates in vivo. Nat Protoc. 2019;14:3333–3365. doi: 10.1038/s41596-019-0222-y. [DOI] [PubMed] [Google Scholar]
  3. Ali F, Taresh S, Al-Nuzaily M, Mok PL, Ismail A, Ahmad S. Stem cells differentiation and probing their therapeutic applications in hematological disorders: a critical review. Eur Rev Med Pharmacol Sci. 2016;20:4390–4400. [PubMed] [Google Scholar]
  4. Allsopp RC, Cheshier S, Weissman IL. Telomere shortening accompanies increased cell cycle activity during serial transplantation of hematopoietic stem cells. J Exp Med. 2001;193:917–924. doi: 10.1084/jem.193.8.917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Asada N, Kunisaki Y, Pierce H, Wang Z, Fernandez NF, Birbrair A, Ma’ayan A, Frenette PS. Differential cytokine contributions of perivascular haematopoietic stem cell niches. Nat Cell Biol. 2017;19:214–223. doi: 10.1038/ncb3475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bai T, Li J, Sinclair A, Imren S, Merriam F, Sun F, O’Kelly MB, Nourigat C, Jain P, Delrow JJ, et al. Expansion of primitive human hematopoietic stem cells by culture in a zwitterionic hydrogel. Nat Med. 2019;25:1566–1575. doi: 10.1038/s41591-019-0601-5. [DOI] [PubMed] [Google Scholar]
  7. Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007;449:1003–1007. doi: 10.1038/nature06196. [DOI] [PubMed] [Google Scholar]
  8. Bergmann A, Steller H. Apoptosis, stem cells, and tissue regeneration. Sci Signal. 2010;3:re8. doi: 10.1126/scisignal.3145re8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Beslu N, Krosl J, Laurin M, Mayotte N, Humphries KR, Sauvageau G. Molecular interactions involved in HOXB4-induced activation of HSC self-renewal. Blood. 2004;104:2307–2314. doi: 10.1182/blood-2004-04-1653. [DOI] [PubMed] [Google Scholar]
  10. Bhardwaj G, Murdoch B, Wu D, Baker DP, Williams KP, Chadwick K, Ling LE, Karanu FN, Bhatia M. Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation. Nat Immunol. 2001;2:172–180. doi: 10.1038/84282. [DOI] [PubMed] [Google Scholar]
  11. Bieging KT, Mello SS, Attardi LD. Unravelling mechanisms of p53-mediated tumour suppression. Nat Rev Cancer. 2014;14:359–370. doi: 10.1038/nrc3711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Blank U, Karlsson S. TGF-β signaling in the control of hematopoietic stem cells. Blood. 2015;125:3542–3550. doi: 10.1182/blood-2014-12-618090. [DOI] [PubMed] [Google Scholar]
  13. Blasco MA. Telomeres and human disease: ageing, cancer and beyond. Nat Rev Genet. 2005;6:611–622. doi: 10.1038/nrg1656. [DOI] [PubMed] [Google Scholar]
  14. Boitano AE, Wang J, Romeo R, Bouchez LC, Parker AE, Sutton S E, Walker JR, Flaveny CA, Perdew GH, Denison MS, et al. Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells. Science. 2010;329:1345–1348. doi: 10.1126/science.1191536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Borggrefe T, Lauth M, Zwijsen A, Huylebroeck D, Oswald F, Giaimo BD. The Notch intracellular domain integrates signals from Wnt, Hedgehog, TGFβ/BMP and hypoxia pathways. Biochim Biophys Acta. 2016;1863:303–313. doi: 10.1016/j.bbamcr.2015.11.020. [DOI] [PubMed] [Google Scholar]
  16. Buttgereit F, Brand MD. A hierarchy of ATP-consuming processes in mammalian cells. Biochem J. 1995;312:163–167. doi: 10.1042/bj3120163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Calvi LM, Link DC. The hematopoietic stem cell niche in homeostasis and disease. Blood. 2015;126:2443–2451. doi: 10.1182/blood-2015-07-533588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC, Martin RP, Schipani E, Divieti P, Bringhurst FR, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003;425:841–846. doi: 10.1038/nature02040. [DOI] [PubMed] [Google Scholar]
  19. Carrelha J, Meng Y, Kettyle LM, Luis TC, Norfo R, Alcolea V, Boukarabila H, Grasso F, Gambardella A, Grover A, et al. Hierarchically related lineage-restricted fates of multipotent haematopoietic stem cells. Nature. 2018;554:106–111. doi: 10.1038/nature25455. [DOI] [PubMed] [Google Scholar]
  20. Casanova-Acebes M, Pitaval C, Weiss LA, Nombela-Arrieta C, Chèvre R, A-González N, Kunisaki Y, Zhang D, van Rooijen N, Silberstein LE, et al. Rhythmic modulation of the hematopoietic niche through neutrophil clearance. Cell. 2013;153:1025–1035. doi: 10.1016/j.cell.2013.04.040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Challen GA, Boles NC, Chambers SM, Goodell MA. Distinct hematopoietic stem cell subtypes are differentially regulated by TGF-β1. Cell Stem Cell. 2010;6:265–278. doi: 10.1016/j.stem.2010.02.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Chen JY, Miyanishi M, Wang SK, Yamazaki S, Sinha R, Kao KS, Seita J, Sahoo D, Nakauchi H, Weissman IL. Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche. Nature. 2016;530:223–227. doi: 10.1038/nature16943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Cheng H, Sun G, Cheng T. Hematopoiesis and microenvironment in hematological malignancies. Cell Regen. 2018;7:22–26. doi: 10.1016/j.cr.2018.08.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Cheng H, Zheng Z, Cheng T. New paradigms on hematopoietic stem cell differentiation. Protein Cell. 2020;11:34–44. doi: 10.1007/s13238-019-0633-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Cheng T. Toward ‘SMART’ stem cells. Gene Ther. 2008;15:67–73. doi: 10.1038/sj.gt.3303066. [DOI] [PubMed] [Google Scholar]
  26. Cheng T, Scadden DT. Cell cycle entry of hematopoietic stem and progenitor cells controlled by distinct cyclin-dependent kinase inhibitors. Int J Hematol. 2002;75:460–465. doi: 10.1007/BF02982107. [DOI] [PubMed] [Google Scholar]
  27. Cheng Y, Luo H, Izzo F, Pickering BF, Nguyen D, Myers R, Schurer A, Gourkanti S, Brüning JC, Vu LP, et al. m6A RNA methylation maintains hematopoietic stem cell identity and symmetric commitment. Cell Rep. 2019;28:1703–1716. doi: 10.1016/j.celrep.2019.07.032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Cheung TH, Rando TA. Molecular regulation of stem cell quiescence. Nat Rev Mol Cell Biol. 2013;14:329–340. doi: 10.1038/nrm3591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Cho IJ, Lui PPW, Obajdin J, Riccio F, Stroukov W, Willis TL, Spagnoli F, Watt FM. Mechanisms, hallmarks, and implications of stem cell quiescence. Stem Cell Rep. 2019;12:1190–1200. doi: 10.1016/j.stemcr.2019.05.012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Christopherson KW, Hangoc G, Mantel CR, Broxmeyer HE. Modulation of hematopoietic stem cell homing and engraftment by CD26. Science. 2004;305:1000–1003. doi: 10.1126/science.1097071. [DOI] [PubMed] [Google Scholar]
  31. Clevers H. What is an adult stem cell. Science. 2015;350:1319–1320. doi: 10.1126/science.aad7016. [DOI] [PubMed] [Google Scholar]
  32. Codispoti B, Makeeva I, Sied J, Benincasa C, Scacco S, Tatullo M. Should we reconsider the apoptosis as a strategic player in tissue regeneration? Int J Biol Sci. 2019;15:2029–2036. doi: 10.7150/ijbs.36362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Cohen S, Roy J, Lachance S, Delisle JS, Marinier A, Busque L, Roy DC, Barabé F, Ahmad I, Bambace N, et al. Hematopoietic stem cell transplantation using single UM171-expanded cord blood: a single-arm, phase 1–2 safety and feasibility study. Lancet Haematol. 2020;7:e134–e145. doi: 10.1016/S2352-3026(19)30202-9. [DOI] [PubMed] [Google Scholar]
  34. Coller HA. The paradox of metabolism in quiescent stem cells. FEBS Lett. 2019;593:2817–2839. doi: 10.1002/1873-3468.13608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Collins K, Mitchell JR. Telomerase in the human organism. Oncogene. 2002;21:564–579. doi: 10.1038/sj.onc.1205083. [DOI] [PubMed] [Google Scholar]
  36. Cui K, Zang C, Roh TY, Schones DE, Childs RW, Peng W, Zhao K. Chromatin signatures in multipotent human hematopoietic stem cells indicate the fate of bivalent genes during differentiation. Cell Stem Cell. 2009;4:80–93. doi: 10.1016/j.stem.2008.11.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. de Lau W, Peng WC, Gros P, Clevers H. The R-spondin/Lgr5/Rnf43 module: regulator of Wnt signal strength. Genes Dev. 2014;28:305–316. doi: 10.1101/gad.235473.113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. DiMascio L, Voermans C, Uqoezwa M, Duncan A, Lu D, Wu J, Sankar U, Reya T. Identification of adiponectin as a novel hemopoietic stem cell growth factor. J Immunol. 2007;178:3511–3520. doi: 10.4049/jimmunol.178.6.3511. [DOI] [PubMed] [Google Scholar]
  39. Ding L, Saunders TL, Enikolopov G, Morrison SJ. Endothelial and perivascular cells maintain haematopoietic stem cells. Nature. 2012;481:457–462. doi: 10.1038/nature10783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Domen J, Cheshier SH, Weissman IL. The role of apoptosis in the regulation of hematopoietic stem cells. J Exp Med. 2000;191:253–264. doi: 10.1084/jem.191.2.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Dong F, Cheng H, Ema H, Cheng T. Probing the fate of transplanted hematopoietic stem cells: is the combinational approach “FIT” for purpose? Sci China Life Sci. 2020;63:1755–1758. doi: 10.1007/s11427-020-1786-4. [DOI] [PubMed] [Google Scholar]
  42. Dong F, Hao S, Zhang S, Zhu C, Cheng H, Yang Z, Hamey FK, Wang X, Gao A, Wang F, et al. Differentiation of transplanted haematopoietic stem cells tracked by single-cell transcriptomic analysis. Nat Cell Biol. 2020;22:630–639. doi: 10.1038/s41556-020-0512-1. [DOI] [PubMed] [Google Scholar]
  43. Duarte D, Hawkins ED, Akinduro O, Ang H, De Filippo K, Kong I Y, Haltalli M, Ruivo N, Straszkowski L, Vervoort SJ, et al. Inhibition of endosteal vascular niche remodeling rescues hematopoietic stem cell loss in AML. Cell Stem Cell. 2018;22:64–77. doi: 10.1016/j.stem.2017.11.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Dulak J, Szade K, Szade A, Nowak W, Józkowicz A. Adult stem cells: hopes and hypes of regenerative medicine. Acta Biochim Pol. 2015;62:329–337. doi: 10.18388/abp.2015_1023. [DOI] [PubMed] [Google Scholar]
  45. Dutta P, Sager HB, Stengel KR, Naxerova K, Courties G, Saez B, Silberstein L, Heidt T, Sebas M, Sun Y, et al. Myocardial infarction activates CCR2+ hematopoietic stem and progenitor cells. Cell Stem Cell. 2015;16:477–487. doi: 10.1016/j.stem.2015.04.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Edlich F. BCL-2 proteins and apoptosis: Recent insights and unknowns. Biochem Biophys Res Commun. 2018;500:26–34. doi: 10.1016/j.bbrc.2017.06.190. [DOI] [PubMed] [Google Scholar]
  47. Fares I, Chagraoui J, Gareau Y, Gingras S, Ruel R, Mayotte N, Csaszar E, Knapp DJHF, Miller P, Ngom M, et al. Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal. Science. 2014;345:1509–1512. doi: 10.1126/science.1256337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Flores I, Benetti R, Blasco MA. Telomerase regulation and stem cell behaviour. Curr Opin Cell Biol. 2006;18:254–260. doi: 10.1016/j.ceb.2006.03.003. [DOI] [PubMed] [Google Scholar]
  49. Fujisaki J, Wu J, Carlson AL, Silberstein L, Putheti P, Larocca R, Gao W, Saito TI, Lo Celso C, Tsuyuzaki H, et al. In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche. Nature. 2011;474:216–219. doi: 10.1038/nature10160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Gao X, Zhang D, Xu C, Li H, Caron KM, Frenette PS. Nociceptive nerves regulate haematopoietic stem cell mobilization. Nature. 2021;589:591–596. doi: 10.1038/s41586-020-03057-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Gao Y, Yang P, Shen H, Yu H, Song X, Zhang L, Zhang P, Cheng H, Xie Z, Hao S, et al. Small-molecule inhibitors targeting INK4 protein p18INK4C enhance ex vivo expansion of haematopoietic stem cells. Nat Commun. 2015;6:6328. doi: 10.1038/ncomms7328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Garcia-Lavandeira M, Diaz-Rodriguez E, Bahar D, Garcia-Rendueles AR, Rodrigues JS, Dieguez C, Alvarez CV. Pituitary cell turnover: from adult stem cell recruitment through differentiation to death. Neuroendocrinology. 2015;101:175–192. doi: 10.1159/000375502. [DOI] [PubMed] [Google Scholar]
  53. Golan K, Kumari A, Kollet O, Khatib-Massalha E, Subramaniam M D, Ferreira ZS, Avemaria F, Rzeszotek S, García-García A, Xie S, et al. Daily onset of light and darkness differentially controls hematopoietic stem cell differentiation and maintenance. Cell Stem Cell. 2018;23:572–585. doi: 10.1016/j.stem.2018.08.002. [DOI] [PubMed] [Google Scholar]
  54. Golan K, Lapidot T. Daily light-and-darkness onset regulates mouse hematopoietic stem cells. Blood Adv. 2019;3:704. doi: 10.1182/bloodadvances.2018027722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Guan JL, Simon AK, Prescott M, Menendez JA, Liu F, Wang F, Wang C, Wolvetang E, Vazquez-Martin A, Zhang J. Autophagy in stem cells. Autophagy. 2013;9:830–849. doi: 10.4161/auto.24132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Hao S, Chen C, Cheng T. Cell cycle regulation of hematopoietic stem or progenitor cells. Int J Hematol. 2016;103:487–497. doi: 10.1007/s12185-016-1984-4. [DOI] [PubMed] [Google Scholar]
  57. Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett NR, Crystal RG, Besmer P, Lyden D, Moore MAS, et al. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell. 2002;109:625–637. doi: 10.1016/S0092-8674(02)00754-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Himburg HA, Muramoto GG, Daher P, Meadows SK, Russell JL, Doan P, Chi JT, Salter AB, Lento WE, Reya T, et al. Pleiotrophin regulates the expansion and regeneration of hematopoietic stem cells. Nat Med. 2010;16:475–482. doi: 10.1038/nm.2119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Himburg HA, Harris JR, Ito T, Daher P, Russell JL, Quarmyne M, Doan PL, Helms K, Nakamura M, Fixsen E, et al. Pleiotrophin regulates the retention and self-renewal of hematopoietic stem cells in the bone marrow vascular niche. Cell Rep. 2012;2:964–975. doi: 10.1016/j.celrep.2012.09.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Hirata Y, Furuhashi K, Ishii H, Li HW, Pinho S, Ding L, Robson S C, Frenette PS, Fujisaki J. CD150high bone marrow Tregs maintain hematopoietic stem cell quiescence and immune privilege via adenosine. Cell Stem Cell. 2018;22:445–453. doi: 10.1016/j.stem.2018.01.017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Ho TT, Warr MR, Adelman ER, Lansinger OM, Flach J, Verovskaya EV, Figueroa ME, Passegué E. Autophagy maintains the metabolism and function of young and old stem cells. Nature. 2017;543:205–210. doi: 10.1038/nature21388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Hoggatt J, Mohammad KS, Singh P, Hoggatt AF, Chitteti BR, Speth JM, Hu P, Poteat BA, Stilger KN, Ferraro F, et al. Differential stem- and progenitor-cell trafficking by prostaglandin E2. Nature. 2013;495:365–369. doi: 10.1038/nature11929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Hoggatt J, Singh P, Tate TA, Chou BK, Datari SR, Fukuda S, Liu L, Kharchenko PV, Schajnovitz A, Baryawno N, et al. Rapid mobilization reveals a highly engraftable hematopoietic stem cell. Cell. 2018;172:191–204. doi: 10.1016/j.cell.2017.11.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Hu L, Zhang Y, Miao W, Cheng T. Reactive oxygen species and Nrf2: Functional and transcriptional regulators of hematopoiesis. Oxid Med Cell Longev. 2019;2019:1–11. doi: 10.1155/2019/5153268. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Itkin T, Ludin A, Gradus B, Gur-Cohen S, Kalinkovich A, Schajnovitz A, Ovadya Y, Kollet O, Canaani J, Shezen E, et al. FGF-2 expands murine hematopoietic stem and progenitor cells via proliferation of stromal cells, c-Kit activation, and CXCL12 down-regulation. Blood. 2012;120:1843–1855. doi: 10.1182/blood-2011-11-394692. [DOI] [PubMed] [Google Scholar]
  66. Itkin T, Gur-Cohen S, Spencer JA, Schajnovitz A, Ramasamy SK, Kusumbe AP, Ledergor G, Jung Y, Milo I, Poulos MG, et al. Distinct bone marrow blood vessels differentially regulate haematopoiesis. Nature. 2016;532:323–328. doi: 10.1038/nature17624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Ito K, Ito K. Hematopoietic stem cell fate through metabolic control. Exp Hematol. 2018;64:1–11. doi: 10.1016/j.exphem.2018.05.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Kikushige Y, Yoshimoto G, Miyamoto T, Iino T, Mori Y, Iwasaki H, Niiro H, Takenaka K, Nagafuji K, Harada M, et al. Human Flt3 is expressed at the hematopoietic stem cell and the granulocyte/macrophage progenitor stages to maintain cell survival. J Immunol. 2008;180:7358–7367. doi: 10.4049/jimmunol.180.11.7358. [DOI] [PubMed] [Google Scholar]
  69. Kollet O, Dar A, Shivtiel S, Kalinkovich A, Lapid K, Sztainberg Y, Tesio M, Samstein RM, Goichberg P, Spiegel A, et al. Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells. Nat Med. 2006;12:657–664. doi: 10.1038/nm1417. [DOI] [PubMed] [Google Scholar]
  70. Korinek V, Barker N, Moerer P, van Donselaar E, Huls G, Peters PJ, Clevers H. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nat Genet. 1998;19:379–383. doi: 10.1038/1270. [DOI] [PubMed] [Google Scholar]
  71. Kunisaki Y, Bruns I, Scheiermann C, Ahmed J, Pinho S, Zhang D, Mizoguchi T, Wei Q, Lucas D, Ito K, et al. Arteriolar niches maintain haematopoietic stem cell quiescence. Nature. 2013;502:637–643. doi: 10.1038/nature12612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Laird DJ, von Andrian UH, Wagers AJ. Stem cell trafficking in tissue development, growth, and disease. Cell. 2008;132:612–630. doi: 10.1016/j.cell.2008.01.041. [DOI] [PubMed] [Google Scholar]
  73. Laurenti E, Göttgens B. From haematopoietic stem cells to complex differentiation landscapes. Nature. 2018;553:418–426. doi: 10.1038/nature25022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Lechman ER, Gentner B, van Galen P, Giustacchini A, Saini M, Boccalatte FE, Hiramatsu H, Restuccia U, Bachi A, Voisin V, et al. Attenuation of miR-126 activity expands HSC in vivo without exhaustion. Cell Stem Cell. 2012;11:799–811. doi: 10.1016/j.stem.2012.09.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Li X, Zhang T, Wilson A, Amarachintha S, Sertorio M, Pang Q. Transcriptional profiling of Foxo3a and Fancd2 regulated genes in mouse hematopoietic stem cells. Genomics Data. 2015;4:148–149. doi: 10.1016/j.gdata.2015.04.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Liu Y, Elf SE, Miyata Y, Sashida G, Liu Y, Huang G, Di Giandomenico S, Lee JM, Deblasio A, Menendez S, et al. p53 regulates hematopoietic stem cell quiescence. Cell Stem Cell. 2009;4:37–48. doi: 10.1016/j.stem.2008.11.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Loeffler D, Wehling A, Schneiter F, Zhang Y, Müller-Bötticher N, Hoppe PS, Hilsenbeck O, Kokkaliaris KD, Endele M, Schroeder T. Asymmetric lysosome inheritance predicts activation of haematopoietic stem cells. Nature. 2019;573:426–429. doi: 10.1038/s41586-019-1531-6. [DOI] [PubMed] [Google Scholar]
  78. Lu R, Czechowicz A, Seita J, Jiang D, Weissman IL. Clonal-level lineage commitment pathways of hematopoietic stem cells in vivo. Proc Natl Acad Sci USA. 2019;116:1447–1456. doi: 10.1073/pnas.1801480116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Lucas D. The bone marrow microenvironment for hematopoietic stem cells. In: Birbrair A, editor. Stem Cell Microenvironments and Beyond. Cham: Springer; 2017. pp. 5–18. [DOI] [PubMed] [Google Scholar]
  80. Lucas D. Leukocyte trafficking and regulation of murine hematopoietic stem cells and their niches. Front Immunol. 2019;10:387. doi: 10.3389/fimmu.2019.00387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Ludin A, Itkin T, Gur-Cohen S, Mildner A, Shezen E, Golan K, Kollet O, Kalinkovich A, Porat Z, D’Uva G, et al. Monocytes-macrophages that express α-smooth muscle actin preserve primitive hematopoietic cells in the bone marrow. Nat Immunol. 2012;13:1072–1082. doi: 10.1038/ni.2408. [DOI] [PubMed] [Google Scholar]
  82. Ludin A, Gur-Cohen S, Golan K, Kaufmann KB, Itkin T, Medaglia C, Lu XJ, Ledergor G, Kollet O, Lapidot T. Reactive oxygen species regulate hematopoietic stem cell self-renewal, migration and development, as well as their bone marrow microenvironment. Antioxid Redox Signal. 2014;21:1605–1619. doi: 10.1089/ars.2014.5941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Luo M, Jeong M, Sun D, Park HJ, Rodriguez BAT, Xia Z, Yang L, Zhang X, Sheng K, Darlington GJ, et al. Long non-coding RNAs control hematopoietic stem cell function. Cell Stem Cell. 2015;16:426–438. doi: 10.1016/j.stem.2015.02.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Maciejewski JP, Risitano A. Hematopoietic stem cells in aplastic anemia. Archives Med Res. 2003;34:520–527. doi: 10.1016/j.arcmed.2003.09.009. [DOI] [PubMed] [Google Scholar]
  85. Magnon C, Frenette PS. StemBook. Cambridge (MA): Harvard Stem Cell Institute; 2008. Hematopoietic stem cell trafficking. [PubMed] [Google Scholar]
  86. Magnon C, Lucas D, Frenette PS. Trafficking of stem cells. In: Filippi MD, Geiger H, editors. Stem Cell Migration. Methods in Molecular Biology (Methods and Protocols) New York: Humana Press; 2011. pp. 3–24. [DOI] [PubMed] [Google Scholar]
  87. Mantel CR, O’Leary HA, Chitteti BR, Huang XX, Cooper S, Hangoc G, Brustovetsky N, Srour EF, Lee MR, Messina-Graham S, et al. Enhancing hematopoietic stem cell transplantation efficacy by mitigating oxygen shock. Cell. 2015;161:1553–1565. doi: 10.1016/j.cell.2015.04.054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. Mao AS, Mooney DJ. Regenerative medicine: Current therapies and future directions. Proc Natl Acad Sci USA. 2015;112:14452–14459. doi: 10.1073/pnas.1508520112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Massberg S, von Andrian UH. Fingolimod and sphingosine-1-phosphate—Modifiers of lymphocyte migration. N Engl J Med. 2006;355:1088–1091. doi: 10.1056/NEJMp068159. [DOI] [PubMed] [Google Scholar]
  90. Matsumoto A, Takeishi S, Kanie T, Susaki E, Onoyama I, Tateishi Y, Nakayama K, Nakayama KI. p57 is required for quiescence and maintenance of adult hematopoietic stem cells. Cell Stem Cell. 2011;9:262–271. doi: 10.1016/j.stem.2011.06.014. [DOI] [PubMed] [Google Scholar]
  91. Mazo IB, Massberg S, von Andrian UH. Hematopoietic stem and progenitor cell trafficking. Trends Immunol. 2011;32:493–503. doi: 10.1016/j.it.2011.06.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  92. McGlincy NJ, Ingolia NT. Transcriptome-wide measurement of translation by ribosome profiling. Methods. 2017;126:112–129. doi: 10.1016/j.ymeth.2017.05.028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  93. Milyavsky M, Gan OI, Trottier M, Komosa M, Tabach O, Notta F, Lechman E, Hermans KG, Eppert K, Konovalova Z, et al. A distinctive DNA damage response in human hematopoietic stem cells reveals an apoptosis-independent role for p53 in self-renewal. Cell Stem Cell. 2010;7:186–197. doi: 10.1016/j.stem.2010.05.016. [DOI] [PubMed] [Google Scholar]
  94. Mohammad K, Dakik P, Medkour Y, Mitrofanova D, Titorenko V I. Quiescence entry, maintenance, and exit in adult stem cells. Int J Mol Sci. 2019;20:2158. doi: 10.3390/ijms20092158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  95. Mohrin M, Bourke E, Alexander D, Warr MR, Barry-Holson K, Le Beau MM, Morrison CG, Passegué E. Hematopoietic stem cell quiescence promotes error-prone DNA repair and mutagenesis. Cell Stem Cell. 2010;7:174–185. doi: 10.1016/j.stem.2010.06.014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  96. Morrison SJ, Kimble J. Asymmetric and symmetric stem-cell divisions in development and cancer. Nature. 2006;441:1068–1074. doi: 10.1038/nature04956. [DOI] [PubMed] [Google Scholar]
  97. Morrison JA, Box AC, McKinney MC, McLennan R, Kulesa P M. Quantitative single cell gene expression profiling in the avian embryo. Dev Dyn. 2015;244:774–784. doi: 10.1002/dvdy.24274. [DOI] [PubMed] [Google Scholar]
  98. Mortensen M, Soilleux EJ, Djordjevic G, Tripp R, Lutteropp M, Sadighi-Akha E, Stranks AJ, Glanville J, Knight S W, Jacobsen SE, et al. The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance. J Exp Med. 2011;208:455–467. doi: 10.1084/jem.20101145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  99. Ni F, Yu WM, Wang X, Fay ME, Young KM, Qiu Y, Lam WA, Sulchek TA, Cheng T, Scadden DT, et al. Ptpn21 controls hematopoietic stem cell homeostasis and biomechanics. Cell Stem Cell. 2019;24:608–620. doi: 10.1016/j.stem.2019.02.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  100. Nitta E, Yamashita M, Hosokawa K, Xian MJ, Takubo K, Arai F, Nakada S, Suda T. Telomerase reverse transcriptase protects ATM-deficient hematopoietic stem cells from ROS-induced apoptosis through a telomere-independent mechanism. Blood. 2011;117:4169–4180. doi: 10.1182/blood-2010-08-297390. [DOI] [PubMed] [Google Scholar]
  101. North TE, Goessling W, Walkley CR, Lengerke C, Kopani KR, Lord AM, Weber GJ, Bowman TV, Jang IH, Grosser T, et al. Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature. 2007;447:1007–1011. doi: 10.1038/nature05883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  102. Papayannopoulou T, Craddock C, Nakamoto B, Priestley GV, Wolf NS. The VLA4/VCAM-1 adhesion pathway defines contrasting mechanisms of lodgement of transplanted murine hemopoietic progenitors between bone marrow and spleen. Proc Natl Acad Sci USA. 1995;92:9647–9651. doi: 10.1073/pnas.92.21.9647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  103. Papayannopoulou T, Scadden DT. Stem-cell ecology and stem cells in motion. Blood. 2008;111:3923–3930. doi: 10.1182/blood-2007-08-078147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  104. Pei W, Feyerabend TB, Rössler J, Wang X, Postrach D, Busch K, Rode I, Klapproth K, Dietlein N, Quedenau C, et al. Polylox barcoding reveals haematopoietic stem cell fates realized in vivo. Nature. 2017;548:456–460. doi: 10.1038/nature23653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  105. Pei W, Shang F, Wang X, Fanti AK, Greco A, Busch K, Klapproth K, Zhang Q, Quedenau C, Sauer S, et al. Resolving fates and single-cell transcriptomes of hematopoietic stem cell clones by polyloxexpress barcoding. Cell Stem Cell. 2020;27:383–395. doi: 10.1016/j.stem.2020.07.018. [DOI] [PubMed] [Google Scholar]
  106. Pierce H, Zhang D, Magnon C, Lucas D, Christin JR, Huggins M, Schwartz GJ, Frenette PS. Cholinergic signals from the CNS regulate G-CSF-mediated HSC mobilization from bone marrow via a glucocorticoid signaling relay. Cell Stem Cell. 2017;20:648–658. doi: 10.1016/j.stem.2017.01.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  107. Pinho S, Frenette PS. Haematopoietic stem cell activity and interactions with the niche. Nat Rev Mol Cell Biol. 2019;20:303–320. doi: 10.1038/s41580-019-0103-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  108. Potten CS. Apoptosis in oral mucosa: lessons from the crypt. A commentary. Oral Dis. 2001;7:81–85. doi: 10.1034/j.1601-0825.2001.70203.x. [DOI] [PubMed] [Google Scholar]
  109. Qian H, Tryggvason K, Jacobsen SE, Ekblom M. Contribution of α6 integrins to hematopoietic stem and progenitor cell homing to bone marrow and collaboration with a4 integrins. Blood. 2006;107:3503–3510. doi: 10.1182/blood-2005-10-3932. [DOI] [PubMed] [Google Scholar]
  110. Qian P, De Kumar B, He XC, Nolte C, Gogol M, Ahn Y, Chen S, Li Z, Xu H, Perry JM, et al. Retinoid-sensitive epigenetic regulation of the Hoxb cluster maintains normal hematopoiesis and inhibits leukemogenesis. Cell Stem Cell. 2018;22:740–754. doi: 10.1016/j.stem.2018.04.012. [DOI] [PubMed] [Google Scholar]
  111. Reya T, Duncan AW, Ailles L, Domen J, Scherer DC, Willert K, Hintz L, Nusse R, Weissman IL. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature. 2003;423:409–414. doi: 10.1038/nature01593. [DOI] [PubMed] [Google Scholar]
  112. Sagot I, Laporte D. Quiescence, an individual journey. Curr Genet. 2019;65:695–699. doi: 10.1007/s00294-018-00928-w. [DOI] [PubMed] [Google Scholar]
  113. Samavarchi-Tehrani P, Samson R, Gingras AC. Proximity dependent biotinylation: key enzymes and adaptation to proteomics approaches. Mol Cell Proteomics. 2020;19:757–773. doi: 10.1074/mcp.R120.001941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  114. Sawai CM, Babovic S, Upadhaya S, Knapp DJHF, Lavin Y, Lau CM, Goloborodko A, Feng J, Fujisaki J, Ding L, et al. Hematopoietic stem cells are the major source of multilineage hematopoiesis in adult animals. Immunity. 2016;45:597–609. doi: 10.1016/j.immuni.2016.08.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  115. Signer RAJ, Magee JA, Salic A, Morrison SJ. Haematopoietic stem cells require a highly regulated protein synthesis rate. Nature. 2014;509:49–54. doi: 10.1038/nature13035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  116. Simsek T, Kocabas F, Zheng J, Deberardinis RJ, Mahmoud AI, Olson EN, Schneider JW, Zhang CC, Sadek HA. The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche. Cell Stem Cell. 2010;7:380–390. doi: 10.1016/j.stem.2010.07.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  117. Sugimura R, He XC, Venkatraman A, Arai F, Box A, Semerad C, Haug JS, Peng L, Zhong XB, Suda T, et al. Noncanonical Wnt signaling maintains hematopoietic stem cells in the niche. Cell. 2012;150:351–365. doi: 10.1016/j.cell.2012.05.041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  118. Sugiyama T, Omatsu Y, Nagasawa T. Niches for hematopoietic stem cells and immune cell progenitors. Int Immunol. 2019;31:5–11. doi: 10.1093/intimm/dxy058. [DOI] [PubMed] [Google Scholar]
  119. Sun J, Ramos A, Chapman B, Johnnidis JB, Le L, Ho YJ, Klein A, Hofmann O, Camargo FD. Clonal dynamics of native haematopoiesis. Nature. 2014;514:322–327. doi: 10.1038/nature13824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  120. Szade K, Gulati GS, Chan CKF, Kao KS, Miyanishi M, Marjon K D, Sinha R, George BM, Chen JY, Weissman IL. Where hematopoietic stem cells live: the bone marrow niche. Antioxid Redox Signal. 2018;29:191–204. doi: 10.1089/ars.2017.7419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  121. Takayama N, Murison A, Takayanagi SI, Arlidge C, Zhou S, Garcia-Prat L, Chan-Seng-Yue M, Zandi S, Gan OI, Boutzen H, et al. The transition from quiescent to activated states in human hematopoietic stem cells is governed by dynamic 3D genome reorganization. Cell Stem Cell. 2021;28:488–501. doi: 10.1016/j.stem.2020.11.001. [DOI] [PubMed] [Google Scholar]
  122. Tokoyoda K, Egawa T, Sugiyama T, Choi BI, Nagasawa T. Cellular niches controlling B lymphocyte behavior within bone marrow during development. Immunity. 2004;20:707–718. doi: 10.1016/j.immuni.2004.05.001. [DOI] [PubMed] [Google Scholar]
  123. Upadhaya S, Sawai CM, Papalexi E, Rashidfarrokhi A, Jang G, Chattopadhyay P, Satija R, Reizis B. Kinetics of adult hematopoietic stem cell differentiation in vivo. J Exp Med. 2018;215:2815–2832. doi: 10.1084/jem.20180136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  124. van Velthoven CTJ, de Morree A, Egner IM, Brett JO, Rando TA. Transcriptional profiling of quiescent muscle stem cells in vivo. Cell Rep. 2017;21:1994–2004. doi: 10.1016/j.celrep.2017.10.037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  125. van Velthoven CTJ, Rando TA. Stem cell quiescence: dynamism, restraint, and cellular idling. Cell Stem Cell. 2019;24:213–225. doi: 10.1016/j.stem.2019.01.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  126. Viatour P, Somervaille TC, Venkatasubrahmanyam S, Kogan S, McLaughlin ME, Weissman IL, Butte AJ, Passegué E, Sage J. Hematopoietic stem cell quiescence is maintained by compound contributions of the retinoblastoma gene family. Cell Stem Cell. 2008;3:416–428. doi: 10.1016/j.stem.2008.07.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  127. Wang W, Yu S, Zimmerman G, Wang Y, Myers J, Yu VWC, Huang D, Huang X, Shim J, Huang Y, et al. Notch receptor-ligand engagement maintains hematopoietic stem cell quiescence and niche retention. Stem Cells. 2015;33:2280–2293. doi: 10.1002/stem.2031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  128. Wang YV, Leblanc M, Fox N, Mao JH, Tinkum KL, Krummel K, Engle D, Piwnica-Worms D, Piwnica-Worms H, Balmain A, et al. Fine-tuning p53 activity through C-terminal modification significantly contributes to HSC homeostasis and mouse radiosensitivity. Genes Dev. 2011;25:1426–1438. doi: 10.1101/gad.2024411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  129. Wei P, Dove KK, Bensard C, Schell JC, Rutter J. The force is strong with this one: metabolism (over)powers stem cell fate. Trends Cell Biol. 2018;28:551–559. doi: 10.1016/j.tcb.2018.02.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  130. Wilkinson AC, Ishida R, Kikuchi M, Sudo K, Morita M, Crisostomo RV, Yamamoto R, Loh KM, Nakamura Y, Watanabe M, et al. Long-term ex vivo haematopoietic-stem-cell expansion allows nonconditioned transplantation. Nature. 2019;571:117–121. doi: 10.1038/s41586-019-1244-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  131. Wilson A, Laurenti E, Oser G, van der Wath RC, Blanco-Bose W, Jaworski M, Offner S, Dunant CF, Eshkind L, Bockamp E, et al. Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair. Cell. 2008;135:1118–1129. doi: 10.1016/j.cell.2008.10.048. [DOI] [PubMed] [Google Scholar]
  132. Winkler IG, Sims NA, Pettit AR, Barbier V, Nowlan B, Helwani F, Poulton IJ, van Rooijen N, Alexander KA, Raggatt LJ, et al. Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs. Blood. 2010;116:4815–4828. doi: 10.1182/blood-2009-11-253534. [DOI] [PubMed] [Google Scholar]
  133. Wojtowicz EE, Lechman ER, Hermans KG, Schoof EM, Wienholds E, Isserlin R, van Veelen PA, Broekhuis MJC, Janssen GMC, Trotman-Grant A, et al. Ectopic miR-125a expression induces long-term repopulating stem cell capacity in mouse and human hematopoietic progenitors. Cell Stem Cell. 2016;19:383–396. doi: 10.1016/j.stem.2016.06.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  134. Xie, X., Cheng, X., Wang, G., Zhang, B., Liu, M., Chen, L., Cheng, H., Hao, S., Zhou, J., Zhu, P., et al. (2021). Single-cell transcriptomes of peripheral blood cells indicate and elucidate severity of COVID-19. Sci China Life Sci doi: 10.1007/s11427-020-1880-y. [DOI] [PMC free article] [PubMed]
  135. Yamashita M, Nitta E, Suda T. Aspp1 preserves hematopoietic stem cell pool integrity and prevents malignant transformation. Cell Stem Cell. 2015;17:23–34. doi: 10.1016/j.stem.2015.05.013. [DOI] [PubMed] [Google Scholar]
  136. Yamashita M, Nitta E, Suda T. Regulation of hematopoietic stem cell integrity through p53 and its related factors. Ann NYAcad Sci. 2016;1370:45–54. doi: 10.1111/nyas.12986. [DOI] [PubMed] [Google Scholar]
  137. Yu H, Shen H, Yuan Y, XuFeng R, Hu X, Garrison SP, Zhang L, Yu J, Zambetti GP, Cheng T. Deletion of Puma protects hematopoietic stem cells and confers long-term survival in response to high-dose γ-irradiation. Blood. 2010;115:3472–3480. doi: 10.1182/blood-2009-10-248278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  138. Yuan L, Sakamoto N, Song G, Sato M. Low-level shear stress induces human mesenchymal stem cell migration through the SDF-1/CXCR4 axis via MAPK signaling pathways. Stem Cells Dev. 2013;22:2384–2393. doi: 10.1089/scd.2012.0717. [DOI] [PubMed] [Google Scholar]
  139. Zhang J, Supakorndej T, Krambs JR, Rao M, Abou-Ezzi G, Ye RY, Li S, Trinkaus K, Link DC. Bone marrow dendritic cells regulate hematopoietic stem/progenitor cell trafficking. J Clin Invest. 2019;129:2920–2931. doi: 10.1172/JCI124829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  140. Zhang Z, Zhu P, Zhou Y, Sheng Y, Hong Y, Xiang D, Qian Z, Mosenson J, Wu WS. A novel slug-containing negativefeedback loop regulates SCF/c-Kit-mediated hematopoietic stem cell self-renewal. Leukemia. 2017;31:403–413. doi: 10.1038/leu.2016.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  141. Zhao M, Ross JT, Itkin T, Perry JM, Venkatraman A, Haug JS, Hembree MJ, Deng CX, Lapidot T, He XC, et al. FGF signaling facilitates postinjury recovery of mouse hematopoietic system. Blood. 2012;120:1831–1842. doi: 10.1182/blood-2011-11-393991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  142. Zhao Y, Zhou J, Liu D, Dong F, Cheng H, Wang W, Pang Y, Wang Y, Mu X, Ni Y, et al. ATF4 plays a pivotal role in the development of functional hematopoietic stem cells in mouse fetal liver. Blood. 2015;126:2383–2391. doi: 10.1182/blood-2015-03-633354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  143. Zhou BO, Yu H, Yue R, Zhao Z, Rios JJ, Naveiras O, Morrison SJ. Bone marrow adipocytes promote the regeneration of stem cells and haematopoiesis by secreting SCF. Nat Cell Biol. 2017;19:891–903. doi: 10.1038/ncb3570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  144. Zhou J, Xu J, Zhang L, Liu S, Ma Y, Wen X, Hao J, Li Z, Ni Y, Li X, et al. Combined single-cell profiling of lncRNAs and functional screening reveals that H19 is pivotal for embryonic hematopoietic stem cell development. Cell Stem Cell. 2019;24:285–298. doi: 10.1016/j.stem.2018.11.023. [DOI] [PubMed] [Google Scholar]

Articles from Science China. Life Sciences are provided here courtesy of Nature Publishing Group

RESOURCES