Language
English
Publication Date
10-28-2025
Journal
Nature Biotechnology
DOI
10.1038/s41587-025-02853-z
PMID
41152623
PMCID
PMC12728835
PubMedCentral® Posted Date
12-25-2025
PubMedCentral® Full Text Version
Author MSS
Abstract
Controlling stem cell differentiation is a longstanding goal in biomedical research. Here we explore how cell fate is influenced by RNA condensates, specifically P-bodies, which modulate gene expression posttranscriptionally. We profiled the transcriptomes of biomolecular condensates in diverse developmental contexts spanning multiple vertebrate species. Our analyses revealed conserved, cell type-specific sequestration of untranslated RNAs encoding cell fate regulators. P-body RNA contents do not reflect active gene expression in each cell type but are enriched for translationally repressed transcripts characteristic of the preceding developmental stage. Mechanistically, P-body contents are controlled by microRNAs and can be profoundly reshaped by perturbing AGO2 or polyadenylation site usage. Applying these insights to stem cell differentiation, we show that manipulating P-body assembly or microRNA activity can direct naive mouse and human pluripotent stem cells toward totipotency or primed human embryonic cells toward the germ cell lineage. Our findings link cell fate decisions to RNA condensates across vertebrates and provide a means of controlling cell identity.
Published Open-Access
yes
Recommended Citation
Pessina, Patrizia; Nevo, Mika; Shi, Junchao; et al., "Selective RNA Sequestration in Biomolecular Condensates Directs Cell Fate Transitions" (2025). Faculty and Staff Publications. 6005.
https://digitalcommons.library.tmc.edu/baylor_docs/6005