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Publication : Capture of Mouse and Human Stem Cells with Features of Formative Pluripotency.

First Author  Kinoshita M Year  2021
Journal  Cell Stem Cell Volume  28
Issue  3 Pages  453-471.e8
PubMed ID  33271069 Mgi Jnum  J:380561
Mgi Id  MGI:6710431 Doi  10.1016/j.stem.2020.11.005
Citation  Kinoshita M, et al. (2021) Capture of Mouse and Human Stem Cells with Features of Formative Pluripotency. Cell Stem Cell 28(3):453-471.e8
abstractText  Pluripotent cells emerge as a naive founder population in the blastocyst, acquire capacity for germline and soma formation, and then undergo lineage priming. Mouse embryonic stem cells (ESCs) and epiblast-derived stem cells (EpiSCs) represent the initial naive and final primed phases of pluripotency, respectively. Here, we investigate the intermediate formative stage. Using minimal exposure to specification cues, we derive stem cells from formative mouse epiblast. Unlike ESCs or EpiSCs, formative stem (FS) cells respond directly to germ cell induction. They colonize somatic tissues and germline in chimeras. Whole-transcriptome analyses show similarity to pre-gastrulation formative epiblast. Signal responsiveness and chromatin accessibility features reflect lineage capacitation. Furthermore, FS cells show distinct transcription factor dependencies, relying critically on Otx2. Finally, FS cell culture conditions applied to human naive cells or embryos support expansion of similar stem cells, consistent with a conserved staging post on the trajectory of mammalian pluripotency.
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