ArticleProtein & cell2016
Role of circadian gene Clock during differentiation of mouse pluripotent stem cells.
Article in Protein & cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Ginsenosides alleviate the progression of hepatic fibrosis by targeting the liver circadian clock geneMolecular medicine reports · 2026Article
- Anti-skin aging effects of black ginseng extracts through regulating inflammatory factors and the CLOCK-ERK pathway in mice.Journal of ginseng research · 2026Article
- Multiomics reveal biomolecular shifts and ER stress in sleep-restricted women affecting NSC functions.iScience · 2025Article
- The mutual impacts of stem cells and sleep: opportunities for improved stem cell therapy.Stem cell research & therapy · 2025Review
- "Time Is out of Joint" in Pluripotent Stem Cells: How and Why.International journal of molecular sciences · 2024Review
- CLOCK inhibits the proliferation of porcine ovarian granulosa cells by targeting ASB9.Journal of animal science and biotechnology · 2023Article
- Generation of CRISPR-Cas9-mediated knockin mutant models in mice and MEFs for studies of polymorphism in clock genes.Scientific reports · 2023Article
- Inhibition of Expression of the Circadian Clock GeneInternational journal of molecular sciences · 2023Article
- Endogenous circadian reporters reveal functional differences ofProceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Relevance of Circadian Clocks to Stem Cell Differentiation and Cancer Progression.NeuroSci · 2022Review
- Review
- Stabilization of heterochromatin by CLOCK promotes stem cell rejuvenation and cartilage regeneration.Cell research · 2021Article
- Multiplexed CRISPR-Cas9 system in a single adeno-associated virus to simultaneously knock out redundant clock genes.Scientific reports · 2021Article
- The Lineage Before Time: Circadian and Nonclassical Clock Influences on Development.Annual review of cell and developmental biology · 2020Review
- The molecular clock protein Bmal1 regulates cell differentiation in mouse embryonic stem cells.Life science alliance · 2020Article
- BMAL1 coordinates energy metabolism and differentiation of pluripotent stem cells.Life science alliance · 2020Article
- Response to Stimulations Inducing Circadian Rhythm in Human Induced Pluripotent Stem Cells.Cells · 2020Article
- Inhibition ofFrontiers in physiology · 2019Article
- Adult stem cell maintenance and tissue regeneration around the clock: do impaired stem cell clocks drive age-associated tissue degeneration?Biogerontology · 2018Review
- Hypophosphatemia Regulates Molecular Mechanisms of Circadian Rhythm.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Biological rhythms controlled by the circadian clock are absent in embryonic stem cells (ESCs). However, they start to develop during the differentiation of pluripotent ESCs to downstream cells. Conversely, biological rhythms in adult somatic cells disappear when they are reprogrammed into induced pluripotent stem cells (iPSCs). These studies indicated that the development of biological rhythms in ESCs might be closely associated with the maintenance and differentiation of ESCs. The core circadian gene Clock is essential for regulation of biological rhythms. Its role in the development of biological rhythms of ESCs is totally unknown. Here, we used CRISPR/CAS9-mediated genetic editing techniques, to completely knock out the Clock expression in mouse ESCs. By AP, teratoma formation, quantitative real-time PCR and Immunofluorescent staining, we did not find any difference between Clock knockout mESCs and wild type mESCs in morphology and pluripotent capability under the pluripotent state. In brief, these data indicated Clock did not influence the maintaining of pluripotent state. However, they exhibited decreased proliferation and increased apoptosis. Furthermore, the biological rhythms failed to develop in Clock knockout mESCs after spontaneous differentiation, which indicated that there was no compensational factor in most peripheral tissues as described in mice models before (DeBruyne et al., 2007b). After spontaneous differentiation, loss of CLOCK protein due to Clock gene silencing induced spontaneous differentiation of mESCs, indicating an exit from the pluripotent state, or its differentiating ability. Our findings indicate that the core circadian gene Clock may be essential during normal mESCs differentiation by regulating mESCs proliferation, apoptosis and activity.
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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.