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Extraneous E-Cadherin Engages the Deterministic Process of Somatic Reprogramming through Modulating STAT3 and Erk1/2

Yu-Hao Liu1, Chien-Chang Chen1, Yi-Jen Hsueh2,3

  • 1Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.

Cells
|February 12, 2021
PubMed

Insights

Scientists discovered that the balance between STAT3 and Erk1/2 activities controls how somatic cells reprogram. Manipulating this ratio, along with E-cadherin levels, can guide cells toward deterministic or stochastic reprogramming pathways.

Area of Science:

  • Cellular reprogramming
  • Stem cell biology
  • Molecular mechanisms

Background:

  • Somatic cell reprogramming into induced pluripotent stem cells (iPSCs) can follow different pathways.
  • The molecular drivers dictating the choice between these reprogramming modes remain largely unelucidated.

Purpose of the Study:

  • To investigate the molecular events governing the selection of reprogramming modes during somatic cell reprogramming.
  • To identify key signaling pathways and factors influencing the initiation of reprogramming.

Main Methods:

  • Analysis of signaling pathway activities, specifically STAT3 and Erk1/2.
  • Investigating the role of E-cadherin in early reprogramming events.
  • Experimental manipulation of signaling pathway ratios in the cellular milieu.

Main Results:

  • The ratio of phosphorylated STAT3 (pSTAT3) to phosphorylated Erk1/2 (pErk1/2) activity reversibly determines the reprogramming mode.
  • A lower pSTAT3/pErk1/2 activity ratio promotes the deterministic reprogramming process.
  • Increased E-cadherin expression facilitates early reprogramming by stabilizing key receptor complexes (LIF/gp130, EGFR/ErbB2).

Conclusions:

  • The pSTAT3/pErk1/2 activity ratio is a critical determinant of reprogramming mode selection.
  • Extraneous E-cadherin can enhance the initiation of somatic reprogramming towards a deterministic pathway.
  • Modulating the signaling environment offers a strategy to direct OSKM-mediated reprogramming outcomes.
Keywords:
Col1a1 4F2A Oct4-GFPinduced pluripotent stem cell (iPSC)reprogrammable mousesomatic reprogrammingstochastic and deterministic model

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