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

Kyoko Ito, Raphaël Turcotte, Jinhua Cui, Samuel E. Zimmerman, Sandra I. 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

100 Scopus citations

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 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 PPAR-fatty acid oxidation promotes to expand 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 mechanisms of HSC expansion, and suggest potential methods of cell fate manipulation through metabolic pathways.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalScience
DOIs
StateAccepted/In press - Oct 13 2016

ASJC Scopus subject areas

  • Medicine(all)
  • General

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    Ito, K., Turcotte, R., Cui, J., Zimmerman, S. E., Pinho, S. I., 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. (Accepted/In press). Self-renewal of a purified Tie2+ hematopoietic stem cell population relies on mitochondrial clearance. Science, 1-10. https://doi.org/10.1126/science.aaf5530