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Lookup NU author(s): Dan Hipps, Dr Angela Pyle, Dr Anna Porter, Philip Dobson, Dr Helen Tuppen, Dr Conor LawlessORCiD, Dr Oliver Russell, Emeritus Professor Doug Turnbull, Professor David Deehan, Professor Gavin Hudson
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2024.Heteroplasmic mitochondrial DNA (mtDNA) variants accumulate as humans age, particularly in the stem-cell compartments, and are an important contributor to age-related disease. Mitochondrial dysfunction has been observed in osteoporosis and somatic mtDNA pathogenic variants have been observed in animal models of osteoporosis. However, this has never been assessed in the relevant human tissue. Mesenchymal stem cells (MSCs) are the progenitors to many cells of the musculoskeletal system and are critical to skeletal tissues and bone vitality. Investigating mtDNA in MSCs could provide novel insights into the role of mitochondrial dysfunction in osteoporosis. To determine if this is possible, we investigated the landscape of somatic mtDNA variation in MSCs through a combination of fluorescence-activated cell sorting and single-cell next-generation sequencing. Our data show that somatic heteroplasmic variants are present in individual patient-derived MSCs, can reach high heteroplasmic fractions and have the potential to be pathogenic. The identification of somatic heteroplasmic variants in MSCs of patients highlights the potential for mitochondrial dysfunction to contribute to the pathogenesis of osteoporosis.
Author(s): Hipps D, Pyle A, Porter ALR, Dobson PF, Tuppen H, Lawless C, Russell OM, Turnbull DM, Deehan DJ, Hudson G
Publication type: Article
Publication status: Published
Journal: Scientific Reports
Year: 2024
Volume: 14
Issue: 1
Print publication date: 01/12/2024
Online publication date: 09/09/2024
Acceptance date: 30/08/2024
Date deposited: 16/09/2024
ISSN (electronic): 2045-2322
Publisher: Nature Research
URL: https://doi.org/10.1038/s41598-024-71822-4
DOI: 10.1038/s41598-024-71822-4
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