Department of Surgery, Division of Vascular and Endovascular Surgery; Diabetes Center of Excellence
Cell Biology | Cellular and Molecular Physiology | Nutritional and Metabolic Diseases | Physiological Processes
Hypercholesterolemia accelerates the phenotypes of aging in hematopoietic stem cells (HSCs). As yet, little is known about the underlying mechanism. We found that hypercholesterolemia downregulates Ten eleven translocation 1 (Tet1) in HSCs. The total HSC population was increased, while the long-term (LT) population, side population and reconstitution capacity of HSCs were significantly decreased in Tet1(-/-) mice. Expression of the Tet1 catalytic domain in HSCs effectively restored the LT population and reconstitution capacity of HSCs isolated from Tet1(-/-) mice. While Tet1 deficiency upregulated the expression of p19 and p21 in HSCs by decreasing the H3K27me3 modification, the restoration of Tet1 activity reduced the expression of p19, p21 and p27 by restoring the H3K27me3 and H3K36me3 modifications on these genes. These results indicate that Tet1 plays a critical role in maintaining the quiescence and reconstitution capacity of HSCs and that hypercholesterolemia accelerates HSC aging phenotypes by decreasing Tet1 expression in HSCs.
Haematopoietic stem cells, Aging, Risk factors
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DOI of Published Version
Tie G, Yan J, Khair L, Tutto A, Messina LM. Hypercholesterolemia Accelerates the Aging Phenotypes of Hematopoietic Stem Cells by a Tet1-Dependent Pathway. Sci Rep. 2020 Feb 27;10(1):3567. doi: 10.1038/s41598-020-60403-w. PMID: 32107419; PMCID: PMC7046636. Link to article on publisher's site
Tie G, Yan J, Khair L, Tutto AA, Messina LM. (2020). Hypercholesterolemia Accelerates the Aging Phenotypes of Hematopoietic Stem Cells by a Tet1-Dependent Pathway. Open Access Articles. https://doi.org/10.1038/s41598-020-60403-w. Retrieved from https://escholarship.umassmed.edu/oapubs/4175
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This work is licensed under a Creative Commons Attribution 4.0 License.