Self-renewal of a purified Tie2+ hematopoietic stem cell population relies on mitochondrial clearance Journal Article


Authors: Ito, K.; Turcotte, R.; Cui, J.; Zimmerman, S. E.; Pinho, S.; Mizoguchi, T.; Arai, F.; Runnels, J. M.; Alt, C.; Teruya-Feldstein, J.; Mar, J. C.; Singh, R.; Suda, T.; Lin, C. P.; Frenette, P. S.; Ito, K.
Article Title: Self-renewal of a purified Tie2+ hematopoietic stem cell population relies on mitochondrial clearance
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. © 2016, American Association for the Advancement of Science. All rights reserved.
Keywords: murinae
Journal Title: Science
Volume: 354
Issue: 6316
ISSN: 0036-8075
Publisher: American Association for the Advancement of Science  
Date Published: 2016-12-02
Start Page: 1156
End Page: 1160
Language: English
DOI: 10.1126/science.aaf5530
PROVIDER: scopus
PMCID: PMC5164878
PUBMED: 27738012
DOI/URL:
Notes: Article -- Export Date: 3 January 2017 -- Source: Scopus
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MSK Authors
  1. Julie T Feldstein
    290 Feldstein
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