Abstract：
:Cell types more advanced in development than embryonic stem cells, such as EpiSCs, fail to contribute to chimeras when injected into pre-implantation-stage blastocysts, apparently because the injected cells undergo apoptosis. Here we show that transient promotion of cell survival through expression of the anti-apoptotic gene BCL2 enables EpiSCs and Sox17+ endoderm progenitors to integrate into blastocysts and contribute to chimeric embryos. Upon injection into blastocyst, BCL2-expressing EpiSCs contributed to all bodily tissues in chimeric animals while Sox17+ endoderm progenitors specifically contributed in a region-specific fashion to endodermal tissues. In addition, BCL2 expression enabled rat EpiSCs to contribute to mouse embryonic chimeras, thereby forming interspecies chimeras that could survive to adulthood. Our system therefore provides a method to overcome cellular compatibility issues that typically restrict chimera formation. Application of this type of approach could broaden the use of embryonic chimeras, including region-specific chimeras, for basic developmental biology research and regenerative medicine.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Masaki H,Kato-Itoh M,Takahashi Y,Umino A,Sato H,Ito K,Yanagida A,Nishimura T,Yamaguchi T,Hirabayashi M,Era T,Loh KM,Wu SM,Weissman IL,Nakauchi Hdoi
10.1016/j.stem.2016.10.013subject
Has Abstractpub_date
2016-11-03 00:00:00pages
587-592issue
5eissn
1934-5909issn
1875-9777pii
S1934-5909(16)30353-8journal_volume
19pub_type
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