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

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103 Citations (Scopus)


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
Issue number6316
Publication statusPublished - Dec 2 2016

All Science Journal Classification (ASJC) codes

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    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. (2016). Self-renewal of a purified Tie2+ hematopoietic stem cell population relies on mitochondrial clearance. Science, 354(6316), 1156-1160.