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Updated: May 9, 2025
07:18
A Simple Method to Identify Kinases That Regulate Embryonic Stem Cell Pluripotency by High-throughput Inhibitor Screening
Published on: May 12, 2017
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ATR regulates OCT4 phosphorylation and safeguards human naïve pluripotency
Xudong Ma1, Cheng Chen2, Xinyu Chen3
1Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, Zhejiang, China.
Scientific Reports
|May 1, 2025
Summary
Researchers found that ATR kinase is crucial for maintaining human naïve pluripotency in stem cells. This kinase phosphorylates OCT4, impacting pluripotency regulation and DNA damage response during early development.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Molecular Biology
Background:
- Human embryonic stem cells (hESCs) can transition between primed and naïve pluripotency states.
- OCT4 is a key pluripotency factor, but its role in human naïve pluripotency is unclear.
Purpose of the Study:
- To investigate the regulatory role of OCT4 phosphorylation in human naïve pluripotency.
- To identify kinases involved in regulating OCT4 phosphorylation in different hESC states.
Main Methods:
- Systematic mapping of OCT4 phosphorylation sites.
- Identification and characterization of kinases targeting OCT4.
- Assessment of ATR kinase activity in naïve versus primed hESCs.
- Analysis of ATR inhibition effects on naïve hESC induction and survival.
Main Results:
- Differential phosphorylation sites on OCT4 were identified between naïve and primed hESCs.
- ATR was identified as a key kinase phosphorylating OCT4 specifically in naïve hESCs.
- ATR kinase activity was higher in naïve hESCs compared to primed hESCs.
- Inhibition of ATR activity impaired naïve hESC induction and increased apoptosis.
Conclusions:
- ATR kinase activity is essential for safeguarding human naïve pluripotency.
- OCT4 phosphorylation by ATR may link DNA damage response pathways to pluripotency regulation.
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