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Cells are the smallest and basic units of life, whether it is a single cell that forms the entire organism, e.g., in a bacterium or trillions of them, e.g., in humans. No matter what organism a cell is a part of, they share specific characteristics.
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Resolving Cell Fate Decisions during Somatic Cell Reprogramming by Single-Cell RNA-Seq.

Lin Guo1, Lihui Lin2, Xiaoshan Wang2

  • 1CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou 510530, China; Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 511436, China; Guangzhou Regenerative Medicine and Health GuangDong Laboratory (GRMH-GDL), Guangzhou 510005, China.

Molecular Cell
|February 18, 2019
PubMed
Summary

Somatic cell reprogramming into induced pluripotent stem cells (iPSCs) is heterogeneous. Our study reveals a cell fate continuum model, identifying key bifurcation points and factors like Klf4 and IFN-γ that influence reprogramming efficiency.

Keywords:
Dppa5aInterferon gammaKlf4Oct4Sox2bifurcationcell fate decisioninduced pluripotent stem cellsreprogrammingsingle-cell RNA sequencing

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In vivo Reprogramming of Adult Somatic Cells to Pluripotency by Overexpression of Yamanaka Factors
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Area of Science:

  • Stem cell biology
  • Cellular reprogramming
  • Developmental biology

Background:

  • Somatic cell reprogramming to induced pluripotent stem cells (iPSCs) is a complex and heterogeneous process.
  • Understanding the cell fate continuum during reprogramming is crucial for improving efficiency and control.

Purpose of the Study:

  • To elucidate the cell fate continuum during somatic cell reprogramming at single-cell resolution.
  • To identify key factors and bifurcation points influencing reprogramming outcomes.

Main Methods:

  • Development of the SOT (Single-cell fate Observation Tool) for analyzing reprogramming.
  • Single-cell analysis of over 150,000 cells from Oct4/Sox2/Klf4 (OSK) and chemical reprogramming.
  • Identification of cell populations based on specific markers (Cd34, Fxyd5, Psca).

Main Results:

  • Somatic cells bifurcate into reprogramming potential (RP) and non-reprogramming (NR) fates.
  • Klf4 promotes a keratinocyte-like NR fate (Cd34+/Fxyd5+/Psca+).
  • Interferon-gamma (IFN-γ) inhibits the transition to pluripotency in RP cells.

Conclusions:

  • A generic bifurcation model for cell fate decisions in somatic cell reprogramming is proposed.
  • This model offers insights into improving reprogramming strategies.
  • Findings may be applicable to other cell fate decision systems.