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Identification and Single-Cell Functional Characterization of an Endodermally Biased Pluripotent Substate in Human Embryonic Stem Cells.

TitleIdentification and Single-Cell Functional Characterization of an Endodermally Biased Pluripotent Substate in Human Embryonic Stem Cells.
Publication TypeJournal Article
Year of Publication2018
AuthorsAllison TF, Smith AG, Anastassiadis K, Sloane-Stanley J, Biga V, Stavish D, Hackland J, Sabri S, Langerman J, Jones M, Plath K, Coca D, Barbaric I, Gokhale P, Andrews PW
JournalStem Cell Reports
Volume10
Issue6
Pagination1895-1907
Date Published2018 Jun 05
ISSN2213-6711
Abstract

Human embryonic stem cells (hESCs) display substantial heterogeneity in gene expression, implying the existence of discrete substates within the stem cell compartment. To determine whether these substates impact fate decisions of hESCs we used a GFP reporter line to investigate the properties of fractions of putative undifferentiated cells defined by their differential expression of the endoderm transcription factor, GATA6, together with the hESC surface marker, SSEA3. By single-cell cloning, we confirmed that substates characterized by expression of GATA6 and SSEA3 include pluripotent stem cells capable of long-term self-renewal. When clonal stem cell colonies were formed from GATA6-positive and GATA6-negative cells, more of those derived from GATA6-positive cells contained spontaneously differentiated endoderm cells than similar colonies derived from the GATA6-negative cells. We characterized these discrete cellular states using single-cell transcriptomic analysis, identifying a potential role for SOX17 in the establishment of the endoderm-biased stem cell state.

DOI10.1016/j.stemcr.2018.04.015
Alternate JournalStem Cell Reports
PubMed ID29779895
PubMed Central IDPMC5993559
Grant ListMR/L012537/1 / / Medical Research Council / United Kingdom
P01 GM099134 / GM / NIGMS NIH HHS / United States
T32 CA009056 / CA / NCI NIH HHS / United States
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