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Metabolism as master of hematopoietic stem cell fate

  • Kyoko Ito
  • Massimo Bonora
  • Keisuke Ito
Progress in Hematology Molecular pathogenesis of leukemia and stem cells

Abstract

HSCs have a fate choice when they divide; they can self-renew, producing new HSCs, or produce daughter cells that will mature to become committed cells. Technical challenges, however, have long obscured the mechanics of these choices. Advances in flow-sorting have made possible the purification of HSC populations, but available HSC-enriched fractions still include substantial heterogeneity, and single HSCs have proven extremely difficult to track and observe. Advances in single-cell approaches, however, have led to the identification of a highly purified population of hematopoietic stem cells (HSCs) that make a critical contribution to hematopoietic homeostasis through a preference for self-renewing division. Metabolic cues are key regulators of this cell fate choice, and the importance of controlling the population and quality of mitochondria has recently been highlighted to maintain the equilibrium of HSC populations. Leukemic cells also demand tightly regulated metabolism, and shifting the division balance of leukemic cells toward commitment has been considered as a promising therapeutic strategy. A deeper understanding of precisely how specific modes of metabolism control HSC fate is, therefore, of great biological interest, and more importantly will be critical to the development of new therapeutic strategies that target HSC division balance for the treatment of hematological disease.

Keywords

Cellular metabolism Mitochondria Hematopoietic stem cell Leukemia Stem cell fate 

Notes

Acknowledgements

We are grateful to members of the Ito lab and Einstein Stem Cell Institute for their comments on HSC self-renewal and metabolisms, and most importantly, to the organizing committee and Dr. Masahiro Kizaki for giving us a great opportunity to present our work at JSH 2017. Ke.I. is supported by grants from the National Institutes of Health (R01DK98263, R01DK115577, and R01DK100689), New York State Department of Health as Core Director of Einstein Single-Cell Genomics/Epigenomics (C029154). Ke.I. is a Research Scholar of the Leukemia and Lymphoma Society. We apologize to the investigators whose work could not be cited owing to space limitations.

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Copyright information

© The Japanese Society of Hematology 2018

Authors and Affiliations

  1. 1.Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine ResearchAlbert Einstein College of MedicineBronxUSA
  2. 2.Departments of Cell Biology and MedicineAlbert Einstein College of MedicineBronxUSA
  3. 3.Albert Einstein Cancer Center and Diabetes Research CenterAlbert Einstein College of MedicineBronxUSA

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