# Unveiling the dynamic drivers: phase separation’s pivotal role in stem cell biology and therapeutic potential

**Authors:** Pei Lin, Yunfan Lin, Ye Lu, Xu Chen, Zihao Zhou, Xinyuan Zhao, Li Cui

PMC · DOI: 10.1186/s13287-025-04403-5 · Stem Cell Research & Therapy · 2025-05-30

## TL;DR

This review explains how phase separation plays a key role in stem cell biology and its potential for developing new therapies.

## Contribution

The paper highlights phase separation's role in stem cells and outlines challenges for translating this knowledge into therapies.

## Key findings

- Phase separation is crucial for cellular organization and impacts gene expression and signaling in stem cells.
- Advanced imaging and real-time analysis are needed to study phase separation dynamics in living systems.
- Understanding phase separation could lead to novel regenerative medicine and disease treatment strategies.

## Abstract

Phase separation is fundamental for cellular organization and function, profoundly impacting a range of biological processes from gene expression to cellular signaling pathways, pivotal in stem cell biology. This review explores the primary types of phase separation and their mechanisms, emphasizing how phase separation is integral to maintaining cellular integrity and its significant implications for disease progression. It elaborates on current insights into how phase separation influences stem cell biology, discussing the challenges in translating these insights into practical applications. These challenges stem from the complex dynamics of phase separation, the need for advanced imaging techniques, and the necessity for real-time, in situ analysis within living systems. Addressing these challenges through innovative methodologies and gaining a deeper understanding of the molecular interactions that govern phase separation in stem cells are essential for developing precise, targeted therapies. Ultimately, advancing our understanding of phase separation could transform stem cell-based therapeutic approaches, opening up novel strategies for disease treatment and advancements in regenerative medicine.

## Full-text entities

- **Genes:** FUS (FUS RNA binding protein) [NCBI Gene 2521] {aka ALS6, ETM4, FUS1, HNRNPP2, POMP75, TLS}, SNHG9 (small nucleolar RNA host gene 9) [NCBI Gene 735301] {aka NCRNA00062}, LCK (LCK proto-oncogene, Src family tyrosine kinase) [NCBI Gene 3932] {aka IMD22, LSK, YT16, p56lck, pp58lck}, SENP1 (SUMO specific peptidase 1) [NCBI Gene 29843] {aka SuPr-2}, SOX2 (SRY-box transcription factor 2) [NCBI Gene 6657] {aka ANOP3, MCOPS3}, CBX1 (chromobox 1) [NCBI Gene 10951] {aka CBX, HP1-BETA, HP1Hs-beta, HP1Hsbeta, Hp1beta, M31}, CBX2 (chromobox 2) [NCBI Gene 84733] {aka CDCA6, M33, SRXY5}, LIN28A (lin-28 RNA binding posttranscriptional regulator A) [NCBI Gene 79727] {aka CSDD1, LIN-28, LIN28, ZCCHC1, lin-28A}, SCMH1 (Scm polycomb group protein homolog 1) [NCBI Gene 22955] {aka Scml3}, POU5F1 (POU class 5 homeobox 1) [NCBI Gene 5460] {aka OCT3, OCT4, OCT4Borf1, OTF-3, OTF3, OTF4}, SQSTM1 (sequestosome 1) [NCBI Gene 8878] {aka A170, DMRV, EBIAP, FTDALS3, NADGP, OSIL}, TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, cpeb1b (cytoplasmic polyadenylation element binding protein 1b) [NCBI Gene 30702] {aka ZOR-1, cepb1b, cpeb1, fd15c06, wu:fd15c06, zorba}, WNK1 (WNK lysine deficient protein kinase 1) [NCBI Gene 65125] {aka HSAN2, HSN2, KDP, PPP1R167, PRKWNK1, PSK}, ABCF1 (ATP binding cassette subfamily F member 1) [NCBI Gene 23] {aka ABC27, ABC50}, HSD17B13 (hydroxysteroid 17-beta dehydrogenase 13) [NCBI Gene 345275] {aka FLDP, HMFN0376, NIIL497, SCDR9, SDR16C3}, AIL6 (AINTEGUMENTA-like 6) [NCBI Gene 830915] {aka AINTEGUMENTA-like 6, F12B17.140, F12B17_140, PLETHORA 3, PLT3}, DDX6 (DEAD-box helicase 6) [NCBI Gene 1656] {aka HLR2, IDDILF, P54, RCK, Rck/p54}, PCLAF (PCNA clamp associated factor) [NCBI Gene 9768] {aka KIAA0101, L5, NS5ATP9, OEATC, OEATC-1, OEATC1}, KDM6A (lysine demethylase 6A) [NCBI Gene 7403] {aka KABUK2, UTX, bA386N14.2}, BMP4 (bone morphogenetic protein 4) [NCBI Gene 652] {aka BMP2B, BMP2B1, MCOPS6, OFC11, ZYME}, BMP1 (bone morphogenetic protein 1) [NCBI Gene 649] {aka OI13, PCOLC, PCP, TLD}, CBX5 (chromobox 5) [NCBI Gene 23468] {aka HEL25, HP1, HP1A, HP1alpha}, ythdf1 (YTH N6-methyladenosine RNA binding protein F1) [NCBI Gene 327606] {aka fb49c02, wu:fb49c02, wu:fi19h06, wu:fj87f09, wu:fp06c11, zgc:55657}, Ythdc1 (YTH domain containing 1) [NCBI Gene 38420] {aka BcDNA:GH01918, CG12076, Dmel\CG12076, YT521, YT521-B, Ythdc}, SFPQ (splicing factor proline and glutamine rich) [NCBI Gene 6421] {aka POMP100, PPP1R140, PSF}, SS18 (SS18 subunit of BAF chromatin remodeling complex) [NCBI Gene 6760] {aka SMARCL1, SSXT, SYT}, DACT1 (dishevelled binding antagonist of beta catenin 1) [NCBI Gene 51339] {aka DAPPER, DAPPER1, DPR1, FRODO, HDPR1, TBS2}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, SMAD7 (SMAD family member 7) [NCBI Gene 4092] {aka CRCS3, MADH7, MADH8}, Mettl3 (Methyltransferase like 3) [NCBI Gene 42844] {aka CG5933, Dm ime4, Dmel\CG5933, IME4, Ime4, MTA70}, XPC (XPC complex subunit, DNA damage recognition and repair factor) [NCBI Gene 7508] {aka RAD4, XP3, XPCC, p125}, FGB (fibrinogen beta chain) [NCBI Gene 2244] {aka HEL-S-78p}, ctnnb1 (catenin (cadherin-associated protein), beta 1) [NCBI Gene 30265] {aka ctnnb, id:ibd2058, wu:fb73e10, wu:fi81c06, wu:fk25h01}, G6PC1 (glucose-6-phosphatase catalytic subunit 1) [NCBI Gene 2538] {aka G6PC, G6PT, G6Pase, GSD1, GSD1a}, MAGEB2 (MAGE family member B2) [NCBI Gene 4113] {aka CT3.2, DAM6, MAGE-XP-2}, PTAFR (platelet activating factor receptor) [NCBI Gene 5724] {aka PAFR}, KMT2B (lysine methyltransferase 2B) [NCBI Gene 9757] {aka CXXC10, DYT28, HRX2, MLL1B, MLL2, MLL4}, BRD4 (bromodomain containing 4) [NCBI Gene 23476] {aka CAP, CDLS6, FSHRG4, HUNK1, HUNKI, MCAP}, CBX7 (chromobox 7) [NCBI Gene 23492], OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) [NCBI Gene 8473] {aka HINCUT-1, HRNT1, MRX106, O-GLCNAC, OGT1, XLID106}, ZSCAN4 (zinc finger and SCAN domain containing 4) [NCBI Gene 201516] {aka ZNF494}, RNF168 (ring finger protein 168) [NCBI Gene 165918] {aka RIDL, hRNF168}, BANF1 (barrier to autointegration nuclear assembly factor 1) [NCBI Gene 8815] {aka BAF, BCRP1, D14S1460, NGPS}, G3BP1 (G3BP stress granule assembly factor 1) [NCBI Gene 10146] {aka G3BP, HDH-VIII}, TOPBP1 (DNA topoisomerase II binding protein 1) [NCBI Gene 11073] {aka Dpb11, TOP2BP1}, PSME3 (proteasome activator subunit 3) [NCBI Gene 10197] {aka HEL-S-283, Ki, PA28-gamma, PA28G, PA28gamma, REG-GAMMA}, NPM1 (nucleophosmin 1) [NCBI Gene 4869] {aka B23, NPM}, glh-1 (ATP-dependent RNA helicase glh-1) [NCBI Gene 172414], CD3E (CD3 epsilon subunit of T-cell receptor complex) [NCBI Gene 916] {aka CD3epsilon, IMD18, T3E, TCRE}, CLOCK (clock circadian regulator) [NCBI Gene 9575] {aka KAT13D, bHLHe8}, SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, shha (sonic hedgehog signaling molecule a) [NCBI Gene 30269] {aka ShhNC, fc83d08, shh, syu, vhh-1, vhh1}, WOX5 (WUSCHEL related homeobox 5) [NCBI Gene 820297] {aka WOX5B, WUSCHEL related homeobox 5, WUSCHEL related homeobox 5B}, SALL4 (spalt like transcription factor 4) [NCBI Gene 57167] {aka DRRS, HSAL4, IVIC, ZNF797}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, CKM (creatine kinase, M-type) [NCBI Gene 1158] {aka CKMM, CPK-M, M-CK}, lin28ab (lin-28 homolog Ab) [NCBI Gene 394066] {aka lin28, lin28a, sb:cb650, zgc:55584}, TRIM33 (tripartite motif containing 33) [NCBI Gene 51592] {aka DDH4, ECTO, PTC7, RFG7, TF1G, TIF1G}, HMGB1 (high mobility group box 1) [NCBI Gene 3146] {aka HMG-1, HMG1, HMG3, SBP-1}
- **Diseases:** tibial aplasia syndrome (MESH:C536482), hematopoietic disorders (MESH:D019337), asthmatic (MESH:D013224), sterility (MESH:D007246), osteosarcoma (MESH:D012516), neurological disease (MESH:D020271), metastasis (MESH:D009362), Parkinson's disease (MESH:D010300), cytotoxicity (MESH:D064420), craniofacial disorders (MESH:D019465), Cancer (MESH:D009369), tumorigenesis (MESH:D063646), age-related diseases (MESH:D010024), craniofacial microsomia (MESH:D006053), chronic liver disease (MESH:D008107), ISCs (MESH:C567703), developmental delays and (MESH:D002658), breast cancer (MESH:D001943), polydactyly (MESH:D017689), brachyphalangy (MESH:C535432), airway inflammation (MESH:D007249), embryonic lethality (MESH:D020964), AML (MESH:D015470), nucleolar dysfunction (MESH:D006331), leukemia (MESH:D007938), metabolism (MESH:D008659), LLPS (MESH:D000210), asthma (MESH:D001249)
- **Chemicals:** glutamine (MESH:D005973), platelet activating factor (MESH:D010972), tyrosine (MESH:D014443), GSK-J4 (MESH:C000593030), hydrogen (MESH:D006859), lipid (MESH:D008055), CGX-635 (MESH:D000077863), 5mC (-), 1'6-hexanediol (MESH:C027765), salt (MESH:D012492), 11,12-EET (MESH:C046783), glycogen (MESH:D006003), Manganese (MESH:D008345), Arg (MESH:D001120), pectin (MESH:D010368), choline (MESH:D002794), glucose (MESH:D005947)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Danio rerio (leopard danio, species) [taxon 7955], Drosophila melanogaster (fruit fly, species) [taxon 7227], C. elegans [taxon 328850], Homo sapiens (human, species) [taxon 9606], Arabidopsis thaliana (mouse-ear cress, species) [taxon 3702]
- **Cell lines:** ESCs — Homo sapiens (Human), Embryonic stem cell (CVCL_UI95)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12123740/full.md

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12123740/full.md

## References

9 references — full list in the complete paper: https://tomesphere.com/paper/PMC12123740/full.md

---
Source: https://tomesphere.com/paper/PMC12123740