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Cell. 2019 May 2;177(4):910-924.e22. doi: 10.1016/j.cell.2019.03.013. Epub 2019 Apr 11.

Human Pluripotency Is Initiated and Preserved by a Unique Subset of Founder Cells.

Author information

1
Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8S 4L8, Canada.
2
Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8S 4L8, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada.
3
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
4
Australian Regenerative Medicine Institute, Monash University, Clayton, VIC 3800, Australia.
5
Australian Regenerative Medicine Institute, Monash University, Clayton, VIC 3800, Australia; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
6
Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8S 4L8, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada. Electronic address: mbhatia@mcmaster.ca.

Abstract

The assembly of organized colonies is the earliest manifestation in the derivation or induction of pluripotency in vitro. However, the necessity and origin of this assemblance is unknown. Here, we identify human pluripotent founder cells (hPFCs) that initiate, as well as preserve and establish, pluripotent stem cell (PSC) cultures. PFCs are marked by N-cadherin expression (NCAD+) and reside exclusively at the colony boundary of primate PSCs. As demonstrated by functional analysis, hPFCs harbor the clonogenic capacity of PSC cultures and emerge prior to commitment events or phenotypes associated with pluripotent reprogramming. Comparative single-cell analysis with pre- and post-implantation primate embryos revealed hPFCs share hallmark properties with primitive endoderm (PrE) and can be regulated by non-canonical Wnt signaling. Uniquely informed by primate embryo organization in vivo, our study defines a subset of founder cells critical to the establishment pluripotent state.

KEYWORDS:

cell fate; founder; human development; non-canonical Wnt signaling; pluripotency; pluripotent state; primate; reprogramming; self-renewal; single cell RNA-seq

PMID:
30982595
DOI:
10.1016/j.cell.2019.03.013

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