The chromatin-associated Sin3B protein is required for hematopoietic stem cell functions in mice

David J. Cantor and Gregory David

Key Points

  • Inactivation of Sin3B in the hematopoietic compartment impairs HSC functions.

  • Sin3B regulates HSC differentiation and quiescence.

Publisher's Note: There is an Inside Blood Commentary on this article in this issue.


Hematopoietic stem cells (HSCs) reside at the top of the hematopoietic hierarchy and are the origin of all blood cells produced throughout an individual’s life. The balance between HSC self-renewal and differentiation is maintained by various intrinsic and extrinsic mechanisms. Among these, the molecular pathways that restrict cell cycle progression are critical to the maintenance of functional HSCs. Alterations in the regulation of cell cycle progression in HSCs invariably lead to the development of hematologic malignancies or bone marrow failure syndromes. Here we report that hematopoietic-specific genetic inactivation of Sin3B, an essential component of the mammalian Sin3–histone deacetylase corepressor complex, severely impairs the competitive repopulation capacity of HSCs. Sin3B-deleted HSCs accumulate and fail to properly differentiate following transplantation. Moreover, Sin3B inactivation impairs HSC quiescence and sensitizes mice to myelosuppressive therapy. Together, these results identify Sin3B as a novel and critical regulator of HSC functions.

  • Submitted June 10, 2016.
  • Accepted October 25, 2016.
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