Evidence map›Paper›PMID 40480219›Full record

ArticleStem cell reports2025

GSK3α negatively regulates GSK3β by decreasing its protein levels and enzymatic activity in mouse embryonic stem cells.

Duo Wang, Xi Chen, Joshua Feng, Xueyuan A Jing, Jiaqi Tang, Jean Paul Chadarevian, Haeyoung Park, Matthew Lee, Fan Feng, Chao Zhang and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Duo WangEli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: duow@usc.edu.
Xi ChenEli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: xichen@caltech.edu.
Joshua FengLoker Hydrocarbon Research Institute & Department of Chemistry, University of Southern California, Los Angeles, CA 90089, USA.
Xueyuan A JingEli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Jiaqi TangLoker Hydrocarbon Research Institute & Department of Chemistry, University of Southern California, Los Angeles, CA 90089, USA.
Jean Paul ChadarevianEli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Haeyoung ParkEli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Matthew LeeEli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Fan FengEli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Chao ZhangLoker Hydrocarbon Research Institute & Department of Chemistry, University of Southern California, Los Angeles, CA 90089, USA.
Qi-Long YingEli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: qying@med.usc.edu.

Funding

Embryonic stem cell self-renewalR01GM129305 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI YING, QILONG · 2018 to 2021
$1.3M
NIGMS NIH HHS R01 GM129305
6 · The paper itself

Abstract

Glycogen synthase kinase 3 (GSK3) is a crucial regulator of cellular processes, including stem cell maintenance and differentiation. Although the roles of the two GSK3 isozymes, GSK3α and GSK3β, are well documented, their specific interactions remain less understood. In this study, we explored the regulatory interplay between GSK3α and GSK3β in mouse embryonic stem cells (mESCs). Using genetic manipulation, small-molecule inhibitors, and biochemical analysis, we found that inhibition of GSK3α kinase activity increases GSK3β protein levels and activity, whereas overexpression of GSK3α reduces GSK3β protein levels and activity. Domain-swapping experiments between the two isozymes identified the glycine-rich region at the N terminus of GSK3α as the key sequence responsible for downregulating GSK3β protein levels. Our findings reveal a novel interaction between GSK3 isozymes, with GSK3α modulating GSK3β activity to maintain the balance between stem cell pluripotency and neural differentiation. This insight may open new pathways for understanding stem cell fate mechanisms and developing GSK3-targeted therapeutic strategies in regenerative medicine.

Indexed as

Glycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaMouse Embryonic Stem CellsAnimalsCell DifferentiationMiceProtein BindingGlycogen Synthase Kinase 3glycogen synthase kinase 3 alphaGlycogen Synthase Kinase 3 betaGsk3b protein, mouseAKT signalingGSK3αGSK3βmouse embryonic stem cellsneural differentiationprotein degradationstem cell self-renewal

Identifiers

PMID40480219
PMCPMC12277826

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.