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Updated: Mar 6, 2026

The use of SC1 Pluripotin to Support mESC Self-renewal in the Absence of LIF
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The use of SC1 Pluripotin to Support mESC Self-renewal in the Absence of LIF

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Depletion of Tcf3 and Lef1 maintains mouse embryonic stem cell self-renewal

Shoudong Ye1,2, Tao Zhang1, Chang Tong2

  • 1Center for Stem Cell and Translational Medicine, School of Life Sciences, Anhui University, Hefei 230601, People's Republic of China.

Biology Open
|March 15, 2017
PubMed

Insights

Dual inhibition of GSK3 and MEK maintains embryonic stem cell (ESC) self-renewal. MEK inhibition suppresses LEF1, a key factor in endoderm specification, aiding ESC maintenance.

Area of Science:

  • Stem Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • Embryonic stem cell (ESC) self-renewal is crucial for development and research.
  • Dual inhibition of glycogen synthase kinase 3 (GSK3) and mitogen-activated protein kinase kinase (MEK) maintains ESC self-renewal.
  • GSK3 inhibition promotes self-renewal by reducing T-cell factor 3 (TCF3) repression of pluripotency genes.

Purpose of the Study:

  • To elucidate the mechanism by which MEK inhibition contributes to ESC self-renewal.
  • To investigate the role of lymphoid enhancer factor 1 (LEF1) in MEK-mediated ESC self-renewal.

Main Methods:

  • Investigated the effect of MEK inhibitors on LEF1 expression in mouse ESCs.
  • Utilized gene knockdown and knockout strategies for LEF1 and TCF3.
  • Performed transcriptome resequencing analysis to identify LEF1-associated pathways.

Main Results:

  • MEK inhibition significantly suppressed LEF1 expression in mouse ESCs.
  • LEF1 depletion partially replicated the self-renewal-promoting effects of MEK inhibitors.
  • Simultaneous depletion of TCF3 and LEF1 allowed for the maintenance of undifferentiated ESCs without external factors.
  • LEF1 was found to be closely associated with endoderm specification in ESCs.

Conclusions:

  • LEF1 plays a significant role in MEK-mediated ESC self-renewal.
  • The combined inhibition of TCF3 and LEF1 is sufficient to maintain ESC pluripotency.
  • Shielding ESCs from differentiative cues, such as those mediated by LEF1, is critical for maintaining the ESC ground state.
Keywords:
DifferentiationEmbryonic stem cellsLEF1Self-renewalTCF3

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