Abstract
We have investigated the role that hemopoietic regulatory molecules may play in mouse embryogenesis prior to the appearance of hemopoietic stem cells or their microenvironments. Using polymerase chain reaction analysis, we detected mRNA transcripts for interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) but not for granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-3 in mouse blastocysts at 3.5 days of gestation. Functional IL-6 protein was also detected in cultured blastocysts as a secreted product, as was an activity consistent with the presence of LIF protein. The expression of IL-6 and LIF in blastocysts prior to hemopoiesis suggests that these proteins may regulate the growth and development of trophoblasts or embryonic stem cells.
Full text
PDF



Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baumann H., Wong G. G. Hepatocyte-stimulating factor III shares structural and functional identity with leukemia-inhibitory factor. J Immunol. 1989 Aug 15;143(4):1163–1167. [PubMed] [Google Scholar]
- Chiu C. P., Lee F. IL-6 is a differentiation factor for M1 and WEHI-3B myeloid leukemic cells. J Immunol. 1989 Mar 15;142(6):1909–1915. [PubMed] [Google Scholar]
- Chiu C. P., Moulds C., Coffman R. L., Rennick D., Lee F. Multiple biological activities are expressed by a mouse interleukin 6 cDNA clone isolated from bone marrow stromal cells. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7099–7103. doi: 10.1073/pnas.85.19.7099. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clegg K. B., Pikó L. Poly(A) length, cytoplasmic adenylation and synthesis of poly(A)+ RNA in early mouse embryos. Dev Biol. 1983 Feb;95(2):331–341. doi: 10.1016/0012-1606(83)90034-9. [DOI] [PubMed] [Google Scholar]
- Gascan H., Moreau J. F., Jacques Y., Soulillou J. P. Response of murine IL3-sensitive cell lines to cytokines of human and murine origin. Lymphokine Res. 1989 Spring;8(1):79–84. [PubMed] [Google Scholar]
- Gauldie J., Richards C., Northemann W., Fey G., Baumann H. IFN beta 2/BSF2/IL-6 is the monocyte-derived HSF that regulates receptor-specific acute phase gene regulation in hepatocytes. Ann N Y Acad Sci. 1989;557:46–59. [PubMed] [Google Scholar]
- Gearing D. P., Gough N. M., King J. A., Hilton D. J., Nicola N. A., Simpson R. J., Nice E. C., Kelso A., Metcalf D. Molecular cloning and expression of cDNA encoding a murine myeloid leukaemia inhibitory factor (LIF). EMBO J. 1987 Dec 20;6(13):3995–4002. doi: 10.1002/j.1460-2075.1987.tb02742.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ikebuchi K., Wong G. G., Clark S. C., Ihle J. N., Hirai Y., Ogawa M. Interleukin 6 enhancement of interleukin 3-dependent proliferation of multipotential hemopoietic progenitors. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9035–9039. doi: 10.1073/pnas.84.24.9035. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnson M. H. The molecular and cellular basis of preimplantation mouse development. Biol Rev Camb Philos Soc. 1981 Aug;56(3):463–498. doi: 10.1111/j.1469-185x.1981.tb00356.x. [DOI] [PubMed] [Google Scholar]
- Krug M. S., Berger S. L. First-strand cDNA synthesis primed with oligo(dT). Methods Enzymol. 1987;152:316–325. doi: 10.1016/0076-6879(87)52036-5. [DOI] [PubMed] [Google Scholar]
- Labastie M. C., Thiery J. P., Le Douarin N. M. Mouse yolk sac and intraembryonic tissues produce factors able to elicit differentiation of erythroid burst-forming units and colony-forming units, respectively. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1453–1456. doi: 10.1073/pnas.81.5.1453. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miyatake S., Otsuka T., Yokota T., Lee F., Arai K. Structure of the chromosomal gene for granulocyte-macrophage colony stimulating factor: comparison of the mouse and human genes. EMBO J. 1985 Oct;4(10):2561–2568. doi: 10.1002/j.1460-2075.1985.tb03971.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miyatake S., Yokota T., Lee F., Arai K. Structure of the chromosomal gene for murine interleukin 3. Proc Natl Acad Sci U S A. 1985 Jan;82(2):316–320. doi: 10.1073/pnas.82.2.316. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moore M. A., Metcalf D. Ontogeny of the haemopoietic system: yolk sac origin of in vivo and in vitro colony forming cells in the developing mouse embryo. Br J Haematol. 1970 Mar;18(3):279–296. doi: 10.1111/j.1365-2141.1970.tb01443.x. [DOI] [PubMed] [Google Scholar]
- Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
- Rappolee D. A., Brenner C. A., Schultz R., Mark D., Werb Z. Developmental expression of PDGF, TGF-alpha, and TGF-beta genes in preimplantation mouse embryos. Science. 1988 Sep 30;241(4874):1823–1825. doi: 10.1126/science.3175624. [DOI] [PubMed] [Google Scholar]
- Regenstreif L. J., Rossant J. Expression of the c-fms proto-oncogene and of the cytokine, CSF-1, during mouse embryogenesis. Dev Biol. 1989 May;133(1):284–294. doi: 10.1016/0012-1606(89)90319-9. [DOI] [PubMed] [Google Scholar]
- Rennick D., Jackson J., Yang G., Wideman J., Lee F., Hudak S. Interleukin-6 interacts with interleukin-4 and other hematopoietic growth factors to selectively enhance the growth of megakaryocytic, erythroid, myeloid, and multipotential progenitor cells. Blood. 1989 May 15;73(7):1828–1835. [PubMed] [Google Scholar]
- Satoh T., Nakamura S., Taga T., Matsuda T., Hirano T., Kishimoto T., Kaziro Y. Induction of neuronal differentiation in PC12 cells by B-cell stimulatory factor 2/interleukin 6. Mol Cell Biol. 1988 Aug;8(8):3546–3549. doi: 10.1128/mcb.8.8.3546. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shrestha K., Hiramoto R. N., Ghanta V. K. Establishment of growth factor-dependent MOPC 104E cell line in vitro. Cell Immunol. 1985 Jan;90(1):24–31. doi: 10.1016/0008-8749(85)90165-0. [DOI] [PubMed] [Google Scholar]
- Smith A. G., Heath J. K., Donaldson D. D., Wong G. G., Moreau J., Stahl M., Rogers D. Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides. Nature. 1988 Dec 15;336(6200):688–690. doi: 10.1038/336688a0. [DOI] [PubMed] [Google Scholar]
- Sonoda Y., Yang Y. C., Wong G. G., Clark S. C., Ogawa M. Analysis in serum-free culture of the targets of recombinant human hemopoietic growth factors: interleukin 3 and granulocyte/macrophage-colony-stimulating factor are specific for early developmental stages. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4360–4364. doi: 10.1073/pnas.85.12.4360. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tanabe O., Akira S., Kamiya T., Wong G. G., Hirano T., Kishimoto T. Genomic structure of the murine IL-6 gene. High degree conservation of potential regulatory sequences between mouse and human. J Immunol. 1988 Dec 1;141(11):3875–3881. [PubMed] [Google Scholar]
- Williams R. L., Hilton D. J., Pease S., Willson T. A., Stewart C. L., Gearing D. P., Wagner E. F., Metcalf D., Nicola N. A., Gough N. M. Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells. Nature. 1988 Dec 15;336(6200):684–687. doi: 10.1038/336684a0. [DOI] [PubMed] [Google Scholar]
- Wong G. G., Witek-Giannotti J. S., Temple P. A., Kriz R., Ferenz C., Hewick R. M., Clark S. C., Ikebuchi K., Ogawa M. Stimulation of murine hemopoietic colony formation by human IL-6. J Immunol. 1988 May 1;140(9):3040–3044. [PubMed] [Google Scholar]
- Yamamori T., Fukada K., Aebersold R., Korsching S., Fann M. J., Patterson P. H. The cholinergic neuronal differentiation factor from heart cells is identical to leukemia inhibitory factor. Science. 1989 Dec 15;246(4936):1412–1416. doi: 10.1126/science.2512641. [DOI] [PubMed] [Google Scholar]
- Yokota T., Lee F., Rennick D., Hall C., Arai N., Mosmann T., Nabel G., Cantor H., Arai K. Isolation and characterization of a mouse cDNA clone that expresses mast-cell growth-factor activity in monkey cells. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1070–1074. doi: 10.1073/pnas.81.4.1070. [DOI] [PMC free article] [PubMed] [Google Scholar]