Related Experiment Video

Updated: Jan 21, 2026

Chemical Reversion of Conventional Human Pluripotent Stem Cells to a Naïve-like State with Improved Multilineage Differentiation Potency
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Chemical Reversion of Conventional Human Pluripotent Stem Cells to a Naïve-like State with Improved Multilineage Differentiation Potency

Published on: June 10, 2018

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Calcium: A New Guardian of Naive Pluripotency

Yuqing Zhu1, Jin Zhang2

  • 1Center for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences & Zhejiang University-University of Edinburgh Joint Institute, Zhejiang University School of Medicine, Hangzhou 310058, China.

Cell Stem Cell
|August 3, 2019
PubMed

Insights

CRISPR screens identified intracellular calcium and nuclear export as key factors in naive pluripotency exit. Combined knockout of Tcf7l1 and Atp2b1 allowed mouse embryonic stem cells to self-renew without LIF and 2i.

Area of Science:

  • Stem cell biology
  • Molecular genetics
  • Cellular signaling

Background:

  • Maintaining pluripotency in mouse embryonic stem cells (mESCs) typically requires specific culture conditions like Leukemia Inhibitory Factor (LIF) and 2i inhibitors.
  • Understanding the molecular mechanisms that regulate the exit from naive pluripotency is crucial for controlling stem cell fate.

Purpose of the Study:

  • To identify novel factors involved in the exit from naive pluripotency in mESCs.
  • To investigate the roles of intracellular calcium and nuclear export in regulating self-renewal.

Main Methods:

  • Utilized a CRISPR mutagenesis screen to systematically disrupt genes in mESCs.
  • Analyzed the impact of genetic modifications on mESC self-renewal and pluripotency markers.
  • Investigated the function of specific identified genes, including Tcf7l1 and the calcium transporter Atp2b1.

Main Results:

  • Identified intracellular calcium levels and nuclear export as critical regulators of naive pluripotency exit.
  • Demonstrated that combined knockout of Tcf7l1 and Atp2b1 enables mESCs to maintain self-renewal independently of LIF and 2i.
  • Discovered a novel pathway influencing stem cell self-renewal.

Conclusions:

  • Intracellular calcium and nuclear export are key determinants of the transition from naive pluripotency.
  • Targeting Tcf7l1 and Atp2b1 offers a new strategy for maintaining mESC self-renewal in simplified culture conditions.
  • This study provides new insights into the molecular control of stem cell pluripotency.

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