Single-cell analysis of bidirectional reprogramming between early embryonic states identify mechanisms of differential lineage plasticities in mice Journal Article

   

Authors:	Garg, V.; Yang, Y.; Nowotschin, S.; Setty, M.; Salataj, E.; Kuo, Y. Y.; Murphy, D.; Sharma, R.; Jang, A.; Polyzos, A.; Pe'er, D.; Apostolou, E.; Hadjantonakis, A. K.
Article Title:	Single-cell analysis of bidirectional reprogramming between early embryonic states identify mechanisms of differential lineage plasticities in mice
Abstract:	Two distinct lineages, pluripotent epiblast (EPI) and primitive (extra-embryonic) endoderm (PrE), arise from common inner cell mass (ICM) progenitors in mammalian embryos. To study how these sister identities are forged, we leveraged mouse embryonic stem (ES) cells and extra-embryonic endoderm (XEN) stem cells—in vitro counterparts of the EPI and PrE. Bidirectional reprogramming between ES and XEN coupled with single-cell RNA and ATAC-seq analyses showed distinct rates, efficiencies, and trajectories of state conversions, identifying drivers and roadblocks of reciprocal conversions. While GATA4-mediated ES-to-iXEN conversion was rapid and nearly deterministic, OCT4-, KLF4-, and SOX2-induced XEN-to-induced pluripotent stem (iPS) reprogramming progressed with diminished efficiency and kinetics. A dominant PrE transcriptional program, safeguarded by GATA4, alongside elevated chromatin accessibility and reduced DNA methylation of the EPI underscored the differential plasticities of the two states. Mapping in vitro to embryo trajectories tracked reprogramming cells in either direction along EPI and PrE in vivo states, without transitioning through the ICM. © 2025 The Authors
Keywords:	es cells; blastocyst; reprogramming; epiblast; primitive endoderm; extra-embryonic endoderm; single-cell analysis; pluripotency; xen cells; lineage plasticity
Journal Title:	Developmental Cell
Volume:	60
Issue:	6
ISSN:	1534-5807
Publisher:	Cell Press
Date Published:	2025-03-24
Start Page:	901
End Page:	917.e12
Language:	English
DOI:	10.1016/j.devcel.2024.11.022
PUBMED:	39729987
PROVIDER:	scopus
PMCID:	PMC11998022
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-105000167777&doi=10.1016%2fj.devcel.2024.11.022&partnerID=40&md5=f7f5db082cd7d7008b212e6b11e3768d
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding authors are Dana Pe'er and Anna-Katerina Hadjantonakis -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/223728