Satb1 regulates the self-renewal of hematopoietic stem cells by promoting quiescence and repressing differentiation commitment

Britta Will, Thomas O. Vogler, Boris Bartholdy, Francine Garrett-Bakelman, Jillian Mayer, Laura Barreyro, Ashley Pandolfi, Tihomira I. Todorova, Ujunwa C. Okoye-Okafor, Robert F. Stanley, Tushar D. Bhagat, Amit Verma, Maria E. Figueroa, Ari Melnick, Michael Roth, Ulrich Steidl

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Abstract

How hematopoietic stem cells (HSCs) coordinate the regulation of opposing cellular mechanisms such as self-renewal and differentiation commitment remains unclear. Here we identified the transcription factor and chromatin remodeler Satb1 as a critical regulator of HSC fate. HSCs lacking Satb1 had defective self-renewal, were less quiescent and showed accelerated lineage commitment, which resulted in progressive depletion of functional HSCs. The enhanced commitment was caused by less symmetric self-renewal and more symmetric differentiation divisions of Satb1-deficient HSCs. Satb1 simultaneously repressed sets of genes encoding molecules involved in HSC activation and cellular polarity, including Numb and Myc, which encode two key factors for the specification of stem-cell fate. Thus, Satb1 is a regulator that promotes HSC quiescence and represses lineage commitment.

Original languageEnglish (US)
Pages (from-to)437-445
Number of pages9
JournalNature Immunology
Volume14
Issue number5
DOIs
StatePublished - May 1 2013

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Will, B., Vogler, T. O., Bartholdy, B., Garrett-Bakelman, F., Mayer, J., Barreyro, L., Pandolfi, A., Todorova, T. I., Okoye-Okafor, U. C., Stanley, R. F., Bhagat, T. D., Verma, A., Figueroa, M. E., Melnick, A., Roth, M., & Steidl, U. (2013). Satb1 regulates the self-renewal of hematopoietic stem cells by promoting quiescence and repressing differentiation commitment. Nature Immunology, 14(5), 437-445. https://doi.org/10.1038/ni.2572