Table 1.
The effect of phase separation on stem cell biology
| Cell type | Regulation | Phase separation | Mechanism | Effects | Ref. |
|---|---|---|---|---|---|
| ESC | CINAP | Preventing NEDD4 from forming condensates | Decreasing YAP1 phosphorylation at Ser128 and YAP1 activation | Impacting endoderm differentiation of mESCs | [40] |
| ESC | Centrosome | Promoting LLPS of destruction complex | Enhancing processing of β-catenin | Promoting Wnt-driven ESC differentiation to mesoderm | [41] |
| mESC | RBD and IDR of LIN28A | Promoting phase-separated condensates of LIN28A and nucleolar proteins | Impacting dynamic nucleolar remodeling | Impacting naive-to-primed pluripotency state conversion | [42] |
| HSPC | / | Pabpc1b phase separation | Promoting Cpeb1b interaction and cytoplasmic polyadenylation of shha mRNA. | Impacting HSPC development | [43] |
| SSC | / | YTHDF1 LLPS | Activating the NF-κB-CCND1 axis | Promoting transdifferentiation of SSC to neural stem cell-like cell | [44] |
| MSC | SHP2E76K mutation | SHP2 LLPS | Leading to SHP2 dissociation from complexes I and III and complex I and III hyperactivation | Promoting malignant transformation from MSC to sarcoma stem-like cells | [45] |
| SSC | Upregulation of CBX2 | CBX2 forming condensates | Regulating chromatin structure | Producing differentiating A1 spermatogonia | [51] |
| ESC | Polycomb | CBX7 Phase separation | Maintaining repressed chromatin | Impairing the ability of ESC to form embryoid bodies and neural progenitor cell | [52] |
| mESC | / | CBX7C and PHC2 form large, low-mobility chromatin-free aggregates | Facilitating PRC1 assembly | Regulating ESC differentiation | [53] |
| Pluripotent cell |
IDR and N-terminal 70aa of SS18 |
SS18 forming microscopic condensates | Mediating BAF assembly | Regulating the transition from pluripotent to somatic states of stem cell | [54] |
| / | Sall4 | Co-phase separation of Tet2/3 with Sall4 to form condensates | Mediating 5mC oxidation on bmp4 promoter, and enabling sufficient BMP signaling | Regulating pharyngeal cartilage development | [55] |
| Myogenic cells | / | Dact1 LLPS propensity to form Dact1 nuclear protein aggregates | Regulating Wnt signaling | Illustrating pathophysiological role in human muscular disease | [57] |
| Neural precursors | / | Prox1 LLPS | Recruiting and concentrating HP1 and inducing heterochromatin compaction | Guaranteeing terminal neuronal differentiation | [58] |
| hBMSC | / | YAP LLPS | Recruiting TAZ and TEAD4 | Regulating osteogenic differentiation | [59] |
| ESC | IDR | Forming UTX phase-separated liquid condensates | Enhancing the H3K4 methylation activity of MLL4 | Impacting ESC differentiation | [60] |
| Germline cell | MAGE-B2 | Reducing G3BP protein levels and suppressing phase separation and SG initiation | Decreasing heat stress | Providing cytoprotection to maintain mammalian spermatogenesis | [61] |
| ESC | RYBP | CTCF phase separation | Promoting inter-A compartment interactions | Improving ESC self-renewal and inhibiting their differentiation toward neural progenitor cells | [65] |
| HSPC | ASXL1 | Involving in paraspeckle formation | Upregulating NEAT1 expression and increasing NONO-NEAT1 interactions | Maintaining repopulating potential of HSPC | [66] |
| / | MIP-1 and MIP-2 | Promoting P granule condensation | Recruiting and balancing essential RNA processing machinery | Regulating key developmental transitions in the germ line | [67] |
| / | LCD of ABCF1 | ABCF1 phase separation | Coactivating OCT4/SOX2 | Regulating stem cell self-renewal | [68] |
| Epiblast cell | Oct4 | Highly expressed Oct4 alleles being closer to nuclear speckles | / | Regualting pluripotency transition | [69] |
| ESC | O-GlcNAcylation of Psme3 |
Decreasing P-body assembly |
/ | Maintenance of ESC pluripotent state | [70] |
| Haematopoietic stem cell | PPIA | Promoting LLPS | Increasing cellular stress resistance | Slowing down stem cell ageing | [75] |
| Mesenchymal progenitor cells | Arg 207 in SGF29 | Promoting SGF29 condensates formation | Precise chromatin engagement Co-activator recruitment | Modulating transcriptional landscapes during aging | [76] |
| ISC | Ime4/ Mettl14 | Promoting the formation of BuGZ condensation | Regulating MAPK pathway | Enhancing ISC proliferation Impacting gut repair and longevity | [77] |
| ESC |
PML PML-NBs |
Promoting TRIM33 puncta formation | Regulating Nodal signaling-directed transcription | Regulating nodal signaling in mESCs | [78] |
| ESC | PSPC1 | Enhancing the formation of transcription condensates | Inhibiting the RNA-induced premature release of Pol II | Promoting polymerase binding and transcription | [79] |
| HSPC | / | Enhancing LLPS puncta of NUP98-HOXA9 | Promoting the formation of transcription factor condensates | Inducing leukaemic transformation | [80] |