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The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance.

TitleThe autophagy protein Atg7 is essential for hematopoietic stem cell maintenance.
Publication TypeJournal Article
Year of Publication2011
AuthorsMortensen M, Soilleux EJ, Djordjevic G, Tripp R, Lutteropp M, Sadighi-Akha E, Stranks AJ, Glanville J, Knight S, Jacobsen S-EW, Kranc KR, Simon AKatharina
JournalJ Exp Med
Date Published2011 Mar 14
KeywordsAnimals, Apoptosis, Autophagy, Cell Proliferation, DNA Damage, Female, Hematopoietic Stem Cells, Male, Mice, Mice, Knockout, Microtubule-Associated Proteins, Mitochondria, Myeloproliferative Disorders, Reactive Oxygen Species, Stem Cells

The role of autophagy, a lysosomal degradation pathway which prevents cellular damage, in the maintenance of adult mouse hematopoietic stem cells (HSCs) remains unknown. Although normal HSCs sustain life-long hematopoiesis, malignant transformation of HSCs leads to leukemia. Therefore, mechanisms protecting HSCs from cellular damage are essential to prevent hematopoietic malignancies. In this study, we crippled autophagy in HSCs by conditionally deleting the essential autophagy gene Atg7 in the hematopoietic system. This resulted in the loss of normal HSC functions, a severe myeloproliferation, and death of the mice within weeks. The hematopoietic stem and progenitor cell compartment displayed an accumulation of mitochondria and reactive oxygen species, as well as increased proliferation and DNA damage. HSCs within the Lin(-)Sca-1(+)c-Kit(+) (LSK) compartment were significantly reduced. Although the overall LSK compartment was expanded, Atg7-deficient LSK cells failed to reconstitute the hematopoietic system of lethally irradiated mice. Consistent with loss of HSC functions, the production of both lymphoid and myeloid progenitors was impaired in the absence of Atg7. Collectively, these data show that Atg7 is an essential regulator of adult HSC maintenance.

Alternate JournalJ. Exp. Med.
PubMed ID21339326
PubMed Central IDPMC3058574
Grant List076113 / / Wellcome Trust / United Kingdom
085475 / / Wellcome Trust / United Kingdom
G0501838 / / Medical Research Council / United Kingdom
G0701335 / / Medical Research Council / United Kingdom
G0801073 / / Medical Research Council / United Kingdom
/ / Biotechnology and Biological Sciences Research Council / United Kingdom
/ / Department of Health / United Kingdom
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