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Updated: Sep 28, 2025
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A Quick and Efficient Method for the Purification of Endoderm Cells Generated from Human Embryonic Stem Cells
Published on: March 3, 2016
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Endogenous ROS production in early differentiation state suppresses endoderm differentiation via transient FOXC1
Sugako Oka1,2, Teruhisa Tsuzuki3,4, Masumi Hidaka5,6
1Frontier Research Center, Fukuoka Dental College, Fukuoka, 814-0193, Japan. sugako@mbr.nifty.com.
Cell Death Discovery
|April 2, 2022
Summary
Endogenous reactive oxygen species (ROS) impair human induced pluripotent stem cell (iPSC) differentiation. Controlling intracellular ROS levels revealed a novel mechanism involving the FOXC1 transcription factor in this process.
Area of Science:
- Cell Biology
- Stem Cell Differentiation
- Oxidative Stress
Background:
- Oxidative stress is crucial for cellular processes, including differentiation, proliferation, and apoptosis.
- Previous studies on oxidative stress in differentiation primarily used exogenous ROS inducers or detected ROS during differentiation, limiting understanding of endogenous ROS roles.
Purpose of the Study:
- To investigate the significance of endogenous reactive oxygen species (ROS) production in human induced pluripotent stem cell (iPSC) differentiation.
- To develop a system for controlling intracellular ROS levels during the initial stages of iPSC differentiation.
Main Methods:
- Engineered a human iPSC system with controlled intracellular ROS levels by modifying the SDHC protein (I69E substitution) in the mitochondrial respiratory chain complex.
- Assessed endoderm differentiation capacity and analyzed the expression of the FOXC1 transcription factor.
- Utilized mitochondrial-targeted catalase as an antioxidant and employed FOXC1 knockdown to evaluate rescue effects.
Main Results:
- Increased endogenous ROS levels due to SDHC modification impaired iPSC endoderm differentiation.
- Overproduction of mitochondrial-targeted catalase reversed the differentiation impairment.
- Transient upregulation of the FOXC1 transcription factor was observed early in differentiation following ROS elevation.
- Knockdown of FOXC1 significantly ameliorated the ROS-induced differentiation defect.
Conclusions:
- Endogenous ROS production in early differentiation stages suppresses human iPSC endoderm differentiation.
- This suppression mechanism is mediated by the transient expression of the FOXC1 transcription factor.
- The developed iPSC system provides a novel tool for studying the role of endogenous ROS in cell differentiation.
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