ArticleStem cells (Dayton, Ohio)2017
Bistable Epigenetic States Explain Age-Dependent Decline in Mesenchymal Stem Cell Heterogeneity.
Article in Stem cells (Dayton, Ohio), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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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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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.
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Who cites it
11 citing papers in PubMed.
- The influence of cell source on the senescence of human mesenchymal stem/stromal cells.Human cell · 2025Review
- An Update on Neuroaging on Earth and in Spaceflight.International journal of molecular sciences · 2025Review
- Unveiling heterogeneity in MSCs: exploring marker-based strategies for defining MSC subpopulations.Journal of translational medicine · 2024Review
- Review
- Inter- and Intrapopulational Heterogeneity of Characteristic Markers in Adult Human Neural Crest-derived Stem Cells.Stem cell reviews and reports · 2022Article
- Senescence in Mesenchymal Stem Cells: Functional Alterations, Molecular Mechanisms, and Rejuvenation Strategies.Frontiers in cell and developmental biology · 2020Review
- DNA methylation aging clocks: challenges and recommendations.Genome biology · 2019Review
- Mesenchymal Stromal/Stem Cells in Regenerative Medicine and Tissue Engineering.Stem cells international · 2018Review
- Current Strategies to Generate Human Mesenchymal Stem Cells In Vitro.Stem cells international · 2018Review
- On the origin and impact of mesenchymal stem cell heterogeneity: new insights and emerging tools for single cell analysis.European cells & materials · 2017Review
- Targeting DNA hypermethylation: Computational modeling of DNA demethylation treatment of acute myeloid leukemia.Epigenetics · 2017Article
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The molecular mechanisms by which heterogeneity, a major characteristic of stem cells, is achieved are yet unclear. We here study the expression of the membrane stem cell antigen-1 (Sca-1) in mouse bone marrow mesenchymal stem cell (MSC) clones. We show that subpopulations with varying Sca-1 expression profiles regenerate the Sca-1 profile of the mother population within a few days. However, after extensive replication in vitro, the expression profiles shift to lower values and the regeneration time increases. Study of the promoter of Ly6a unravels that the expression level of Sca-1 is related to the promoter occupancy by the activating histone mark H3K4me3. We demonstrate that these findings can be consistently explained by a computational model that considers positive feedback between promoter H3K4me3 modification and gene transcription. This feedback implicates bistable epigenetic states which the cells occupy with an age-dependent frequency due to persistent histone (de-)modification. Our results provide evidence that MSC heterogeneity, and presumably that of other stem cells, is associated with bistable epigenetic states and suggest that MSCs are subject to permanent state fluctuations. Stem Cells 2017;35:694-704.
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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.