The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance
Open accessAbstract
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.
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Autophagy is essential for maintenance of HSC quiescence.
“This suggests that autophagy is essential for maintenance of HSC quiescence122.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [122]
mTOR is a key controller of ROS levels and autophagy in HSCs.
“For example, the mTOR pathway has been shown to be a major regulator of both ROS levels and autophagy in HSCs20,78,80, (Fig. 3).”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [78]
Mice without autophagy in their haematopoietic system display a prematurely aged haematopoietic system.
“Mice without autophagy in their haematopoietic system display a prematurely aged haematopoietic system [106].”
From Evolution of the immune system in humans from infancy to old age (2015) · cites this paper as [106]
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How neutrophils meet their end
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- Authors
- Mortensen, M., Soilleux, E. J., Djordjevic, G., Tripp, R., Lutteropp, M., Sadighi-Akha, E., Stranks, A. J., Glanville, J., Knight, S., W. Jacobsen, S.-E., Kranc, K. R., & Simon, A. K.
- Affiliations
- Centre for Human Genetics (GB)
- Nuffield Department of Clinical Medicine 1 , 2 , and 3 ; 4 ; and 5 and 6
- University of Glasgow (GB)
- Corresponding author
- Simon, Anna Katharina
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2011-02-21
- Volume
- 208
- Issue
- 3
- Pages
- 455-467
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC3058574
- OpenAlex
- W2136331786
- Cited by
- 657
- References
- 66
- Citations by year
- 2026: 25 · 2025: 31 · 2024: 26 · 2023: 37 · 2022: 48 · 2021: 76 · 2020: 50 · 2019: 37 · 2018: 50 · 2017: 42 · 2016: 54 · 2015: 48 · 2014: 37 · 2013: 46 · 2012: 30
- FWCI
- 28.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc-sa)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Apollo
- Funders
- Wellcome Trust (085475, 076113)
- National Institute for Health and Care Research
- Biotechnology and Biological Sciences Research Council (BB/G021422/1)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- ATG7, autophagy, hematopoietic stem cells, HSC maintenance, conditional gene deletion, myeloproliferation, reactive oxygen species, mitochondrial accumulation, DNA damage, LSK cells, hematopoietic recovery, leukemia prevention, hematopoietic progenitor cells
- MeSH terms
- Autophagy-Related Protein 7, Animals, Autophagy, DNA Damage, Female, Hematopoietic Stem Cells, Male, Microtubule-Associated Proteins, Mitochondria, Myeloproliferative Disorders, Stem Cells, Apoptosis, Reactive Oxygen Species, Mice, Knockout, Cell Proliferation, Mice
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