Self-renewal of a purified Tie2 + hematopoietic stem cell population relies on mitochondrial clearance
- 2 December 2016
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 354 (6316), 1156-1160
- https://doi.org/10.1126/science.aaf5530
Abstract
A single hematopoietic stem cell (HSC) is capable of reconstituting hematopoiesis and maintaining homeostasis by balancing self-renewal and cell differentiation. The mechanisms of HSC division balance, however, are not yet defined. Here we demonstrate, by characterizing at the single-cell level a purified and minimally heterogeneous murine Tie2+ HSC population, that these top hierarchical HSCs preferentially undergo symmetric divisions. The induction of mitophagy, a quality control process in mitochondria, plays an essential role in self-renewing expansion of Tie2+ HSCs. Activation of the PPAR (peroxisome proliferator–activated receptor)–fatty acid oxidation pathway promotes expansion of Tie2+ HSCs through enhanced Parkin recruitment in mitochondria. These metabolic pathways are conserved in human TIE2+ HSCs. Our data thus identify mitophagy as a key mechanism of HSC expansion and suggest potential methods of cell-fate manipulation through metabolic pathways.Funding Information
- NYSTEM (New York State Stem Cell Science) (C029154)
- Harvard Stem Cell Institute
- Ellison Medical Foundation
- NIH (R01DK98263, R01DK100689)
- Leukemia Lymphoma Society
- Japan Society for the Promotion of Science
This publication has 59 references indexed in Scilit:
- A PML–PPAR-δ pathway for fatty acid oxidation regulates hematopoietic stem cell maintenanceNature Medicine, 2012
- Fiji: an open-source platform for biological-image analysisNature Methods, 2012
- In vivo imaging of transplanted hematopoietic stem and progenitor cells in mouse calvarium bone marrowNature Protocols, 2010
- Genetic Animal Models of Parkinson's DiseaseNeuron, 2010
- Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivoProceedings of the National Academy of Sciences, 2009
- FOXO3a-dependent regulation of Pink1 (Park6) mediates survival signaling in response to cytokine deprivationProceedings of the National Academy of Sciences, 2009
- IFNα activates dormant haematopoietic stem cells in vivoNature, 2009
- Live-animal tracking of individual haematopoietic stem/progenitor cells in their nicheNature, 2008
- Imaging Hematopoietic Precursor Division in Real TimeCell Stem Cell, 2007
- Transgenic mice with hematopoietic and lymphoid specific expression of CreEuropean Journal of Immunology, 2003