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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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The pluripotent stem cell-specific transcript ESRG is dispensable for human pluripotency.

Kazutoshi Takahashi1,2, Michiko Nakamura1, Chikako Okubo1

  • 1Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.

Plos Genetics
|May 25, 2021
PubMed
Summary
This summary is machine-generated.

Human endogenous retrovirus-H (HERV-H) long non-coding RNAs like ESRG are not essential for maintaining pluripotency in human pluripotent stem cells (PSCs). ESRG deficiency does not impact PSC identity, differentiation, or reprogramming capabilities.

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Area of Science:

  • Stem cell biology
  • Genomics
  • Epigenetics

Background:

  • Human endogenous retrovirus-H (HERV-H) elements are abundant in the human genome and expressed in human pluripotent stem cells (PSCs).
  • HERV-H derived long non-coding RNAs (lncRNAs) are implicated in maintaining PSC identity and neural differentiation, but their specific functions remain unclear.
  • ESRG is a prominent HERV-H-driven lncRNA highly expressed in PSCs and silenced upon differentiation.

Purpose of the Study:

  • To investigate the functional necessity of the HERV-H-driven lncRNA, ESRG, in human pluripotent stem cells.
  • To determine if ESRG plays a role in maintaining pluripotency and differentiation potential.
  • To assess the impact of ESRG loss-of-function on cellular reprogramming.

Main Methods:

  • CRISPR/Cas9 mediated complete excision of the ESRG gene.
  • Global transcriptome analysis of ESRG-deficient PSCs.
  • Assessment of trilineage differentiation potential.
  • Reprogramming assays using OCT3/4, SOX2, and KLF4 in ESRG-deficient cells.

Main Results:

  • Complete excision of ESRG did not affect the maintenance of either primed or naïve pluripotent states in PSCs.
  • ESRG deficiency had minimal impact on global gene expression profiles of PSCs.
  • ESRG-deficient PSCs maintained trilineage differentiation potential and could be reprogrammed into induced PSCs (iPSCs).

Conclusions:

  • The HERV-H-driven lncRNA ESRG is dispensable for the maintenance of human pluripotency.
  • ESRG is not required for the differentiation capacity of PSCs or their ability to be reprogrammed.
  • These findings clarify the role of specific HERV-H elements in stem cell biology.