Conversion from mouse embryonic to extra-embryonic endoderm stem cells reveals distinct differentiation capacities of pluripotent stem cell states Journal Article

   

Authors:	Cho, L. T. Y.; Wamaitha, S. E.; Tsai, I. J.; Artus, J.; Sherwood, R. I.; Pedersen, R. A.; Hadjantonakis, A. K.; Niakan, K. K.
Article Title:	Conversion from mouse embryonic to extra-embryonic endoderm stem cells reveals distinct differentiation capacities of pluripotent stem cell states
Abstract:	The inner cell mass of the mouse pre-implantation blastocyst comprises epiblast progenitor and primitive endoderm cells of which cognate embryonic (mESCs) or extra-embryonic (XEN) stem cell lines can be derived. Importantly, each stem cell type retains the defining properties and lineage restriction of their in vivo tissue of origin. Recently, we demonstrated that XEN-like cells arise within mESC cultures. This raises the possibility that mESCs can generate self-renewing XEN cells without the requirement for gene manipulation. We have developed a novel approach to convert mESCs to XEN cells (cXEN) using growth factors. We confirm that the downregulation of the pluripotency transcription factor Nanog and the expression of primitive endoderm-associated genes Gata6, Gata4, Sox17 and Pdgfra are necessary for cXEN cell derivation. This approach highlights an important function for Fgf4 in cXEN cell derivation. Paracrine FGF signalling compensates for the loss of endogenous Fgf4, which is necessary to exit mESC selfrenewal, but not for XEN cell maintenance. Our cXEN protocol also reveals that distinct pluripotent stem cells respond uniquely to differentiation promoting signals. cXEN cells can be derived from mESCs cultured with Erk and Gsk3 inhibitors (2i), and LIF, similar to conventional mESCs. However, we find that epiblast stem cells (EpiSCs) derived from the post-implantation embryo are refractory to cXEN cell establishment, consistent with the hypothesis that EpiSCs represent a pluripotent state distinct from mESCs. In all, these findings suggest that the potential of mESCs includes the capacity to give rise to both extra-embryonic and embryonic lineages. © 2012. Published by The Company of Biologists Ltd.
Keywords:	controlled study; nonhuman; animal cell; mouse; animals; mice; mice, knockout; animal tissue; cells, cultured; receptor, platelet-derived growth factor alpha; gene expression; models, biological; embryo; embryonic stem cell; animal experiment; gene function; cell renewal; cell differentiation; cell lineage; mice, transgenic; gene expression regulation, developmental; nucleotide sequence; paracrine signaling; embryonic stem cells; down regulation; pluripotent stem cell; pluripotent stem cells; growth factor; transcription factor nanog; endoderm; mouse embryo; implantation; directed differentiation; transcription factor gata 4; transcription factor gata 6; transcription factor sox17; extra-embryonic endoderm; ectoderm; gata6 transcription factor; bone morphogenetic protein 4; paracrine communication; tretinoin; fgf; hmgb proteins; fibroblast growth factor 4; activins; soxf transcription factors; gata4 transcription factor
Journal Title:	Development
Volume:	139
Issue:	16
ISSN:	0950-1991
Publisher:	Company of Biologists
Date Published:	2012-08-01
Start Page:	2866
End Page:	2877
Language:	English
DOI:	10.1242/dev.078519
PROVIDER:	scopus
PMCID:	PMC3403099
PUBMED:	22791892
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84864317362&partnerID=40&md5=424670f57939a0ce73f4485c0f6f4818
Notes:	--- - "Export Date: 4 September 2012" - "CODEN: DEVPE" - "Molecular Sequence Numbers: GENBANK: GSE38477;" - "Source: Scopus"

https://synapse.mskcc.org/synapse/works/has_related_data_chk/33271