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The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
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Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
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Sox2 modulation increases naïve pluripotency plasticity.

Kathryn C Tremble1,2, Giuliano G Stirparo1, Lawrence E Bates1

  • 1Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.

Iscience
|March 5, 2021
PubMed
Summary
This summary is machine-generated.

Minimal Sox2 expression allows naive pluripotent stem cells (nPSCs) to self-renew and differentiate into all embryonic lineages. Sox2-low nPSCs gain plasticity, differentiating into both embryonic and extraembryonic cell types.

Keywords:
Biological SciencesCell BiologyStem Cells Research

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Area of Science:

  • Stem cell biology
  • Developmental biology
  • Epigenetics

Background:

  • Naive pluripotent stem cells (nPSCs) are crucial for early development.
  • Understanding the regulation of nPSC self-renewal and differentiation is key to regenerative medicine.
  • Sox2 is a known transcription factor involved in pluripotency and differentiation.

Purpose of the Study:

  • To investigate the role of Sox2 expression levels in nPSC self-renewal and differentiation.
  • To determine if reduced Sox2 expression impacts nPSC developmental potential.
  • To explore the molecular mechanisms underlying Sox2-mediated regulation of pluripotency.

Main Methods:

  • Generation and culture of Sox2-low nPSCs.
  • In vitro differentiation assays into embryonic germ lineages.
  • In vivo differentiation studies.
  • Single-cell gene expression analysis.
  • Chromatin immunoprecipitation to assess Oct4 binding.

Main Results:

  • Self-renewal of nPSCs requires only minimal Sox2 expression (Sox2-low).
  • Sox2-low nPSCs maintain neuroectoderm specification and efficient in vitro differentiation into all embryonic germ lineages.
  • Upon removal of self-renewal cues, Sox2-low nPSCs differentiate into both embryonic and extraembryonic cell fates in vitro and in vivo.
  • Sox2-low nPSCs exhibit a naive molecular signature but show increased trophoblast identity and reduced Oct4 binding to naive regulatory elements.

Conclusions:

  • Wild-type levels of Sox2 restrict the developmental potential of nPSCs.
  • Perturbing the naive pluripotency network by reducing Sox2 expression enhances cell plasticity.
  • This finding opens new avenues for controlling cell fate decisions and increasing developmental potential.