ArticleDevelopmental cell2017
A Chemical-Genetic Approach Reveals the Distinct Roles of GSK3α and GSK3β in Regulating Embryonic Stem Cell Fate.
Article in Developmental cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- A universal 6iL/E4 culture system for deriving and maintaining embryonic stem cells across mammalian species.Cell research · 2026Article
- GSK3α functions as a stemness checkpoint across multiple stem cell states.Cell research · 2026Article
- Review
- Article
- Discovery of a CNS active GSK3 degrader using orthogonally reactive linker screening.Nature communications · 2025Article
- GSK3α negatively regulates GSK3β by decreasing its protein levels and enzymatic activity in mouse embryonic stem cells.Stem cell reports · 2025Article
- LIF Promotes Sec15b-Mediated STAT3 Exosome Secretion to Maintain Stem Cell Pluripotency in Mouse Embryonic Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- A novel chemical genetic approach reveals paralog-specific role of ERK1/2 in mouse embryonic stem cell fate control.Frontiers in cell and developmental biology · 2024Article
- Article
- Interactomes of Glycogen Synthase Kinase-3 Isoforms.Journal of proteome research · 2023Article
- Reactivity-based chemical-genetic study of protein kinases.RSC medicinal chemistry · 2022Review
- GSK3α: An Important Paralog in Neurodegenerative Disorders and Cancer.Biomolecules · 2020Review
- Article
- PI3K in stemness regulation: from development to cancer.Biochemical Society transactions · 2020Review
- Inhibition of Wnt/β-Catenin Signaling in Neuroendocrine Tumors in vitro: Antitumoral Effects.Cancers · 2020Article
- Salmonella Effector SteE Converts the Mammalian Serine/Threonine Kinase GSK3 into a Tyrosine Kinase to Direct Macrophage Polarization.Cell host & microbe · 2020Article
- GSK3β Plays a Negative Role During White Spot Syndrome Virus (WSSV) Infection by Regulating NF-κB Activity in ShrimpFrontiers in immunology · 2020Article
- Characterisation of protein isoforms encoded by the Drosophila Glycogen Synthase Kinase 3 gene shaggy.PloS one · 2020Article
- Regenerative medicine: could Parkinson's be the first neurodegenerative disease to be cured?Future science OA · 2019Review
- Wnt/Beta-Catenin Signaling Regulation and a Role for Biomolecular Condensates.Developmental cell · 2019Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Glycogen synthase kinase 3 (GSK3) plays a central role in diverse cellular processes. GSK3 has two mammalian isozymes, GSK3α and GSK3β, whose functions remain ill-defined because of a lack of inhibitors that can distinguish between the two highly homologous isozymes. Here, we show that GSK3α and GSK3β can be selectively inhibited in mouse embryonic stem cells (ESCs) using a chemical-genetic approach. Selective inhibition of GSK3β is sufficient to maintain mouse ESC self-renewal, whereas GSK3α inhibition promotes mouse ESC differentiation toward neural lineages. Genome-wide transcriptional analysis reveals that GSK3α and GSK3β have distinct sets of downstream targets. Furthermore, selective inhibition of individual GSK3 isozymes yields distinct phenotypes from gene deletion, highlighting the power of the chemical-genetic approach in dissecting kinase catalytic functions from the protein's scaffolding functions. Our study opens new avenues for defining GSK3 isozyme-specific functions in various cellular processes.
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Registered trials
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.