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

Kyoko Ito, Raphaël Turcotte, Jinhua Cui, Samuel E. Zimmerman, Sandra Pinho, Toshihide Mizoguchi, Fumio Arai, Judith M. Runnels, Clemens Alt, Julie Teruya-Feldstein, Jessica C. Mar, Rajat Singh, Toshio Suda, Charles P. Lin, Paul S. Frenette, Keisuke Ito

Research output: Contribution to journalArticle

89 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1156-1160
Number of pages5
JournalScience
Volume354
Issue number6316
DOIs
Publication statusPublished - Dec 2 2016
Externally publishedYes

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Hematopoietic Stem Cells
Mitochondrial Degradation
Metabolic Networks and Pathways
Population
Mitochondria
Peroxisome Proliferator-Activated Receptors
Hematopoiesis
Quality Control
Cell Division
Cell Differentiation
Homeostasis
Fatty Acids

All Science Journal Classification (ASJC) codes

  • General

Cite this

Ito, K., Turcotte, R., Cui, J., Zimmerman, S. E., Pinho, S., Mizoguchi, T., ... Ito, K. (2016). Self-renewal of a purified Tie2+ hematopoietic stem cell population relies on mitochondrial clearance. Science, 354(6316), 1156-1160. https://doi.org/10.1126/science.aaf5530

Self-renewal of a purified Tie2+ hematopoietic stem cell population relies on mitochondrial clearance. / Ito, Kyoko; Turcotte, Raphaël; Cui, Jinhua; Zimmerman, Samuel E.; Pinho, Sandra; Mizoguchi, Toshihide; Arai, Fumio; Runnels, Judith M.; Alt, Clemens; Teruya-Feldstein, Julie; Mar, Jessica C.; Singh, Rajat; Suda, Toshio; Lin, Charles P.; Frenette, Paul S.; Ito, Keisuke.

In: Science, Vol. 354, No. 6316, 02.12.2016, p. 1156-1160.

Research output: Contribution to journalArticle

Ito, K, Turcotte, R, Cui, J, Zimmerman, SE, Pinho, S, Mizoguchi, T, Arai, F, Runnels, JM, Alt, C, Teruya-Feldstein, J, Mar, JC, Singh, R, Suda, T, Lin, CP, Frenette, PS & Ito, K 2016, 'Self-renewal of a purified Tie2+ hematopoietic stem cell population relies on mitochondrial clearance', Science, vol. 354, no. 6316, pp. 1156-1160. https://doi.org/10.1126/science.aaf5530
Ito K, Turcotte R, Cui J, Zimmerman SE, Pinho S, Mizoguchi T et al. Self-renewal of a purified Tie2+ hematopoietic stem cell population relies on mitochondrial clearance. Science. 2016 Dec 2;354(6316):1156-1160. https://doi.org/10.1126/science.aaf5530
Ito, Kyoko ; Turcotte, Raphaël ; Cui, Jinhua ; Zimmerman, Samuel E. ; Pinho, Sandra ; Mizoguchi, Toshihide ; Arai, Fumio ; Runnels, Judith M. ; Alt, Clemens ; Teruya-Feldstein, Julie ; Mar, Jessica C. ; Singh, Rajat ; Suda, Toshio ; Lin, Charles P. ; Frenette, Paul S. ; Ito, Keisuke. / Self-renewal of a purified Tie2+ hematopoietic stem cell population relies on mitochondrial clearance. In: Science. 2016 ; Vol. 354, No. 6316. pp. 1156-1160.
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