publication . Article . Other literature type . 2017

autophagy maintains the metabolism and function of young and old stem cells

Ho, Theodore T.; Warr, Matthew R.; Adelman, Emmalee R.; Lansinger, Olivia M.; Flach, Johanna; Verovskaya, Evgenia V.; Figueroa, Maria E.; Passegué, Emmanuelle;
Open Access
  • Published: 01 Mar 2017 Journal: Nature, volume 543, pages 205-210 (issn: 0028-0836, eissn: 1476-4687, Copyright policy)
  • Publisher: Springer Science and Business Media LLC
Abstract
With age, hematopoietic stem cells (HSCs) lose their ability to regenerate the blood system, and promote disease development. Autophagy is associated with health and longevity, and is critical for protecting HSCs from metabolic stress. Here, we show that loss of autophagy in HSCs causes accumulation of mitochondria and an activated metabolic state, which drives accelerated myeloid differentiation mainly through epigenetic deregulations, and impairs HSC self-renewal activity and regenerative potential. Strikingly, the majority of HSCs in aged mice share these altered metabolic and functional features. However, ~ 1/3 of aged HSCs exhibit high autophagy levels and ...
Subjects
Medical Subject Headings: hemic and immune systems
free text keywords: Immunology, Biology, Haematopoiesis, Cell biology, Cell Self Renewal, Stem cell, Ageing, Autophagy, Respiration.status, Mitochondrion, Metabolism, Article
Funded by
NIH| STRUCTURAL BIOLOGY TRAINING PROGRAM
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5T32GM008284-09
  • Funding stream: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
,
NIH| Role of autophagy in normal and transformed hematopoietic stem cells
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 7R01CA184014-04
  • Funding stream: NATIONAL CANCER INSTITUTE
,
NIH| ISLET PRODUCTION FACILITY CORE
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5P30DK063720-03
  • Funding stream: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
,
NIH| Epigenetic biomarkers of response to Azacytidine in Myelodysplastic Syndromes
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01HL126947-04
  • Funding stream: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
,
NIH| Research Training in Biogerontology
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 2T32AG000114-26
  • Funding stream: NATIONAL INSTITUTE ON AGING
41 references, page 1 of 3

Niccoli, T, Partridge, L. Ageing as a risk factor for disease. Curr Biol. 2012; 22: R741-752 [PubMed]

Rando, TA. Stem cells, ageing and the quest for immortality. Nature. 2006; 441: 1080-1086 [OpenAIRE] [PubMed]

López-Otín, C, Blasco, MA, Partridge, L, Serrano, M, Kroemer, G. The hallmarks of aging. Cell. 2013; 153: 1194-1217 [OpenAIRE] [PubMed]

Orkin, SH, Zon, LI. Hematopoiesis: an evolving paradigm for stem cell biology. Cell. 2008; 132: 631-644 [OpenAIRE] [PubMed]

Kohli, L, Passegué, E. Surviving change: the metabolic journey of hematopoietic stem cells. Trends Cell Biol. 2014; 24: 479-487 [OpenAIRE] [PubMed]

Geiger, H, de Haan, G, Florian, MC. The ageing haematopoietic stem cell compartment. Nat Rev Immunol. 2013; 13: 376-389 [PubMed]

Ergen, AV, Boles, NC, Goodell, MA. Rantes/Ccl5 influences hematopoietic stem cell subtypes and causes myeloid skewing. Blood. 2012; 119: 2500-2509 [OpenAIRE] [PubMed]

Kusumbe, AP. Age-dependent modulation of vascular niches for haematopoietic stem cells. Nature. 2016; 532: 380-384 [OpenAIRE] [PubMed]

He, C, Klionsky, DJ. Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet. 2009; 43: 67-93 [OpenAIRE] [PubMed]

Liu, F. FIP200 is required for the cell-autonomous maintenance of fetal hematopoietic stem cells. Blood. 2010; 116: 4806-4814 [OpenAIRE] [PubMed]

Mortensen, M. The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance. J Exp Med. 2011; 208: 455-467 [OpenAIRE] [PubMed]

Leveque-El Mouttie, L. Autophagy is required for stem cell mobilization by G-CSF. Blood. 2015; 125: 2933-2936 [OpenAIRE] [PubMed]

Warr, MR. FOXO3A directs a protective autophagy program in haematopoietic stem cells. Nature. 2013; 494: 323-327 [OpenAIRE] [PubMed]

Rubinsztein, DC, Marino, G, Kroemer, G. Autophagy and aging. Cell. 2011; 146: 682-695 [OpenAIRE] [PubMed]

Garcia-Prat, L. Autophagy maintains stemness by preventing senescence. Nature. 2016; 529: 37-42 [OpenAIRE] [PubMed]

41 references, page 1 of 3
Abstract
With age, hematopoietic stem cells (HSCs) lose their ability to regenerate the blood system, and promote disease development. Autophagy is associated with health and longevity, and is critical for protecting HSCs from metabolic stress. Here, we show that loss of autophagy in HSCs causes accumulation of mitochondria and an activated metabolic state, which drives accelerated myeloid differentiation mainly through epigenetic deregulations, and impairs HSC self-renewal activity and regenerative potential. Strikingly, the majority of HSCs in aged mice share these altered metabolic and functional features. However, ~ 1/3 of aged HSCs exhibit high autophagy levels and ...
Subjects
Medical Subject Headings: hemic and immune systems
free text keywords: Immunology, Biology, Haematopoiesis, Cell biology, Cell Self Renewal, Stem cell, Ageing, Autophagy, Respiration.status, Mitochondrion, Metabolism, Article
Funded by
NIH| STRUCTURAL BIOLOGY TRAINING PROGRAM
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5T32GM008284-09
  • Funding stream: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
,
NIH| Role of autophagy in normal and transformed hematopoietic stem cells
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 7R01CA184014-04
  • Funding stream: NATIONAL CANCER INSTITUTE
,
NIH| ISLET PRODUCTION FACILITY CORE
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5P30DK063720-03
  • Funding stream: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
,
NIH| Epigenetic biomarkers of response to Azacytidine in Myelodysplastic Syndromes
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01HL126947-04
  • Funding stream: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
,
NIH| Research Training in Biogerontology
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 2T32AG000114-26
  • Funding stream: NATIONAL INSTITUTE ON AGING
41 references, page 1 of 3

Niccoli, T, Partridge, L. Ageing as a risk factor for disease. Curr Biol. 2012; 22: R741-752 [PubMed]

Rando, TA. Stem cells, ageing and the quest for immortality. Nature. 2006; 441: 1080-1086 [OpenAIRE] [PubMed]

López-Otín, C, Blasco, MA, Partridge, L, Serrano, M, Kroemer, G. The hallmarks of aging. Cell. 2013; 153: 1194-1217 [OpenAIRE] [PubMed]

Orkin, SH, Zon, LI. Hematopoiesis: an evolving paradigm for stem cell biology. Cell. 2008; 132: 631-644 [OpenAIRE] [PubMed]

Kohli, L, Passegué, E. Surviving change: the metabolic journey of hematopoietic stem cells. Trends Cell Biol. 2014; 24: 479-487 [OpenAIRE] [PubMed]

Geiger, H, de Haan, G, Florian, MC. The ageing haematopoietic stem cell compartment. Nat Rev Immunol. 2013; 13: 376-389 [PubMed]

Ergen, AV, Boles, NC, Goodell, MA. Rantes/Ccl5 influences hematopoietic stem cell subtypes and causes myeloid skewing. Blood. 2012; 119: 2500-2509 [OpenAIRE] [PubMed]

Kusumbe, AP. Age-dependent modulation of vascular niches for haematopoietic stem cells. Nature. 2016; 532: 380-384 [OpenAIRE] [PubMed]

He, C, Klionsky, DJ. Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet. 2009; 43: 67-93 [OpenAIRE] [PubMed]

Liu, F. FIP200 is required for the cell-autonomous maintenance of fetal hematopoietic stem cells. Blood. 2010; 116: 4806-4814 [OpenAIRE] [PubMed]

Mortensen, M. The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance. J Exp Med. 2011; 208: 455-467 [OpenAIRE] [PubMed]

Leveque-El Mouttie, L. Autophagy is required for stem cell mobilization by G-CSF. Blood. 2015; 125: 2933-2936 [OpenAIRE] [PubMed]

Warr, MR. FOXO3A directs a protective autophagy program in haematopoietic stem cells. Nature. 2013; 494: 323-327 [OpenAIRE] [PubMed]

Rubinsztein, DC, Marino, G, Kroemer, G. Autophagy and aging. Cell. 2011; 146: 682-695 [OpenAIRE] [PubMed]

Garcia-Prat, L. Autophagy maintains stemness by preventing senescence. Nature. 2016; 529: 37-42 [OpenAIRE] [PubMed]

41 references, page 1 of 3
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publication . Article . Other literature type . 2017

autophagy maintains the metabolism and function of young and old stem cells

Ho, Theodore T.; Warr, Matthew R.; Adelman, Emmalee R.; Lansinger, Olivia M.; Flach, Johanna; Verovskaya, Evgenia V.; Figueroa, Maria E.; Passegué, Emmanuelle;