Abstract：
:Trophoblast stem cells (TSCs) arise from the first cell fate decision in the developing embryo and generate extra-embryonic lineages, giving rise to the fetal portion of the placenta. Mouse embryonic and extra-embryonic lineages are strictly separated by a distinct epigenetic barrier, which is not fully overcome following expression of TSC-determining factors in embryonic stem cells. Here, we show that transient expression of Tfap2c, Gata3, Eomes, and Ets2 is sufficient to reprogram mouse embryonic fibroblasts and post-natal tail-tip-derived fibroblasts into induced TSCs (iTSCs) and surmount the epigenetic barrier separating somatic from extra-embryonic lineages. iTSCs share nearly identical morphological characteristics, gene expression profiles, and DNA methylation patterns with blastocyst-derived TSCs. Furthermore, iTSCs display transgene-independent self-renewal, differentiate along extra-embryonic lineages, and chimerize host placentas following blastocyst injection. These findings provide insights into the transcription factor networks governing TSC identity and opportunities for studying the epigenetic barriers underlying embryonic and extra-embryonic lineage segregation.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Kubaczka C,Senner CE,Cierlitza M,Araúzo-Bravo MJ,Kuckenberg P,Peitz M,Hemberger M,Schorle Hdoi
10.1016/j.stem.2015.08.005subject
Has Abstractpub_date
2015-11-05 00:00:00pages
557-68issue
5eissn
1934-5909issn
1875-9777pii
S1934-5909(15)00360-4journal_volume
17pub_type
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