Inherited pathogenic mitochondrial DNA mutations and gastrointestinal stem cell populations.
J Pathol
; 246(4): 427-432, 2018 12.
Article
em En
| MEDLINE
| ID: mdl-30146801
ABSTRACT
Inherited mitochondrial DNA (mtDNA) mutations cause mitochondrial disease, but mtDNA mutations also occur somatically and accumulate during ageing. Studies have shown that the mutation load of some inherited mtDNA mutations decreases over time in blood, suggesting selection against the mutation. However, it is unknown whether such selection occurs in other mitotic tissues, and where it occurs within the tissue. Gastrointestinal epithelium is a canonical mitotic tissue rapidly renewed by stem cells. Intestinal crypts (epithelium) undergo monoclonal conversion with a single stem cell taking over the niche and producing progeny. We show (1) that there is a significantly lower mtDNA mutation load in the mitotic epithelium of the gastrointestinal tract when compared to the smooth muscle in the same tissue in patients with the pathogenic m.3243A>G and m.8344A>G mutations; (2) that there is considerable variation seen in individual crypts, suggesting changes in the stem cell population; (3) that this lower mutation load is reflected in the absence of a defect in oxidative phosphorylation in the epithelium. This suggests that there is selection against inherited mtDNA mutations in the gastrointestinal stem cells that is in marked contrast to the somatic mtDNA mutations that accumulate with age in epithelial stem cells leading to a biochemical defect. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
DNA Mitocondrial
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Miopatias Mitocondriais
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Células Epiteliais
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Mucosa Gástrica
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Mucosa Intestinal
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Mitocôndrias
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Mutação
Tipo de estudo:
Observational_studies
Limite:
Adult
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
J Pathol
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Reino Unido