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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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Stem cell research aims to find ways to use stem cells to regenerate and repair cellular damage. Over time, most adult cells undergo the wear and tear of aging and lose their ability to divide and repair themselves. Stem cells do not display a particular morphology or function. Adult stem cells, which exist as a small subset of cells in most tissues, keep dividing and can differentiate into a number of specialized cells generally formed by that tissue. These cells enable the body to renew and...
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Cell Competition Eliminates Aneuploid Human Pluripotent Stem Cells.

Amanda Ya1,2, Chenhui Deng1,2, Kristina M Godek1,2,3

  • 1Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.

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PubMed
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Human pluripotent stem cells (hPSCs) tolerate aneuploidy through cell competition. Myc and p53 levels determine survival, maintaining genome stability in these vital cells.

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Mycaneuploidycell competitionhuman embryonic stem cellshuman pluripotent stem cellsmosaicp53preimplantation

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Area of Science:

  • Cell Biology
  • Genetics
  • Developmental Biology

Background:

  • Human pluripotent stem cells (hPSCs) maintain genomic stability despite high rates of mitotic errors causing aneuploidy.
  • Mechanisms preventing proliferation of aneuploid cells in hPSCs are largely unknown.
  • Aneuploidy typically inhibits proliferation in non-transformed somatic cells.

Purpose of the Study:

  • To investigate the mechanisms by which hPSCs maintain genome integrity in the presence of aneuploidy.
  • To understand the role of cell competition in eliminating aneuploid hPSCs.
  • To explore the influence of Myc and p53 in aneuploid hPSC selection.

Main Methods:

  • Comparative analysis of homogeneous and mosaic aneuploid hPSC populations.
  • Assessment of cell proliferation and competition dynamics.
  • Investigation of Myc and p53 expression levels in diploid versus aneuploid hPSCs.

Main Results:

  • Homogeneous aneuploid hPSCs proliferate, unlike aneuploid somatic cells.
  • Mosaic populations exhibit cell non-autonomous competition, eliminating less fit aneuploid cells.
  • Aneuploid hPSCs with altered Myc/p53 levels are outcompeted or gain selective advantage based on relative abundance.

Conclusions:

  • hPSCs tolerate frequent chromosome missegregation and aneuploidy.
  • Myc- and p53-driven cell competition mechanisms preserve genome integrity in hPSCs.
  • Findings impact regenerative medicine applications and understanding diploid human embryo establishment.