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Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
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Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
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Reprogramming progressive cells display low CAG promoter activity.

Xiao Hu1,2, Qiao Wu1,2, Jian Zhang1,2

  • 1Department of Cell Biology, Yale University, New Haven, Connecticut, USA.

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|October 19, 2020
PubMed
Summary
This summary is machine-generated.

Cell reprogramming efficiency varies. This study identifies small cell size and rapid cell cycles, linked to MKL1/SRF activity, as key factors. Low CAG promoter activity cells can be enriched for efficient reprogramming.

Keywords:
CAG promoterMKL1/SRF signalingYamanaka reprogrammingcell cycle speedcell size

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Area of Science:

  • Cell biology
  • Molecular biology
  • Stem cell research

Background:

  • Somatic cell reprogramming into pluripotency using Yamanaka factors exhibits significant variability.
  • Identifying and enriching cells with high reprogramming potential is a persistent challenge in the field.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying variability in cellular reprogramming propensity.
  • To develop a practical method for prospectively isolating cells that reprogram more efficiently.

Main Methods:

  • Analysis of MKL1/SRF transcription factor activity in relation to reprogramming efficiency.
  • Correlation of reprogramming propensity with cell size and cell cycle dynamics.
  • Utilizing the activity of the CAG synthetic promoter to identify and sort cells.

Main Results:

  • Reprogramming variability is associated with MKL1/SRF transcription factor activity, smaller cell size, and faster cell cycles.
  • Cells with low CAG promoter activity (CAGlow) are identified as having higher reprogramming potential.
  • CAGlow cells emerge and proliferate during the initial stages of reprogramming in both mouse and human fibroblasts.

Conclusions:

  • The MKL1/SRF pathway and cell cycle dynamics play crucial roles in determining reprogramming efficiency.
  • Low CAG promoter activity serves as a reliable marker for identifying and enriching cells with enhanced reprogramming capabilities.
  • This finding offers a practical strategy for improving the efficiency of induced pluripotent stem cell generation.