ArticleThe Journal of biological chemistry2014
Unfolded protein response is required for the definitive endodermal specification of mouse embryonic stem cells via Smad2 and β-catenin signaling.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Reduced osteogenic factors and early osteoblast senescence in SOD1(G93A) ALS mouse model.JCI insight · 2026Article
- GRP94 is indispensable for definitive endoderm specification of human induced pluripotent stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- A neurodegeneration checkpoint mediated by REST protects against the onset of Alzheimer's disease.Nature communications · 2023Article
- Emerging roles of endoplasmic reticulum stress in the cellular plasticity of cancer cells.Frontiers in oncology · 2023Review
- A possible connection between reactive oxygen species and the unfolded protein response in lens development: From insight to foresight.Frontiers in cell and developmental biology · 2022Review
- Sequential Defects in Cardiac Lineage Commitment and Maturation Cause Hypoplastic Left Heart Syndrome.Circulation · 2021Article
- A small molecule modulating monounsaturated fatty acids and Wnt signaling confers maintenance to induced pluripotent stem cells against endodermal differentiation.Stem cell research & therapy · 2021Article
- Endoplasmic reticulum stress inhibits 3D Matrigel-induced vasculogenic mimicry of breast cancer cells via TGF-β1/Smad2/3 and β-catenin signaling.FEBS open bio · 2021Article
- Histone crotonylation promotes mesoendodermal commitment of human embryonic stem cells.Cell stem cell · 2021Article
- Post-Transcriptional Regulation of Homeostatic, Stressed, and Malignant Stem Cells.Cell stem cell · 2020Review
- Article
- The Best for the Most Important: Maintaining a Pristine Proteome in Stem and Progenitor Cells.Stem cells international · 2019Review
- AIMP3 depletion causes genome instability and loss of stemness in mouse embryonic stem cells.Cell death & disease · 2018Article
- ER stress regulates alkaline phosphatase gene expression in vascular smooth muscle cells via an ATF4-dependent mechanism.BMC research notes · 2018Article
- High Glucose Inhibits Neural Stem Cell Differentiation Through Oxidative Stress and Endoplasmic Reticulum Stress.Stem cells and development · 2018Article
- In vitro culture expansion impairs chondrogenic differentiation and the therapeutic effect of mesenchymal stem cells by regulating the unfolded protein response.Journal of biological engineering · 2018Article
- Mechanisms of protein homeostasis (proteostasis) maintain stem cell identity in mammalian pluripotent stem cells.Cellular and molecular life sciences : CMLS · 2018Review
- Novel KDM1A inhibitors induce differentiation and apoptosis of glioma stem cells via unfolded protein response pathway.Oncogene · 2017Article
- New insights into the unfolded protein response in stem cells.Oncotarget · 2016Review
- Influence of Amino Acid Metabolism on Embryonic Stem Cell Function and Differentiation.Advances in nutrition (Bethesda, Md.) · 2016Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tremendous efforts have been made to elucidate the molecular mechanisms that control the specification of definitive endoderm cell fate in gene knockout mouse models and ES cell (ESC) differentiation models. However, the impact of the unfolded protein response (UPR), because of the stress of the endoplasmic reticulum on endodermal specification, is not well addressed. We employed UPR-inducing agents, thapsigargin and tunicamycin, in vitro to induce endodermal differentiation of mouse ESCs. Apart from the endodermal specification of ESCs, Western blotting demonstrated the enhanced phosphorylation of Smad2 and nuclear translocation of β-catenin in ESC-derived cells. The inclusion of the endoplasmic reticulum stress inhibitor tauroursodeoxycholic acid to the induction cultures prevented the differentiation of ESCs into definitive endodermal cells even when Activin A was supplemented. Also, the addition of the TGF-β inhibitor SB431542 and the Wnt/β-catenin antagonist IWP-2 negated the endodermal differentiation of ESCs mediated by thapsigargin and tunicamycin. These data suggest that the activation of the UPR appears to orchestrate the induction of the definitive endodermal cell fate of ESCs via both the Smad2 and β-catenin signaling pathways. The prospective regulatory machinery may be helpful for directing ESCs to differentiate into definitive endodermal cells for cellular therapy in the future.
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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.