UMMS Affiliation

Department of Surgery, Division of Vascular and Endovascular Surgery; Diabetes Center of Excellence

Publication Date

2020-02-27

Document Type

Article

Disciplines

Cell Biology | Cellular and Molecular Physiology | Nutritional and Metabolic Diseases | Physiological Processes

Abstract

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.

Keywords

Haematopoietic stem cells, Aging, Risk factors

Rights and Permissions

Copyright © The Author(s) 2020. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

DOI of Published Version

10.1038/s41598-020-60403-w

Source

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

Journal/Book/Conference Title

Scientific reports

Related Resources

Link to Article in PubMed

PubMed ID

32107419

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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