Satb1 regulates hematopoietic stem cell self-renewal by promoting quiescence and repressing differentiation commitment

How hematopoietic stem cells coordinate the regulation of opposing cellular mechanisms like self-renewal and differentiation commitment remains unclear. Here, we identified the transcription factor and chromatin remodeler Satb1 as a critical regulator of the hematopoietic stem cell (HSC) fate. HSCs...

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Detalles Bibliográficos
Autores principales: Will, Britta, Vogler, Thomas O., Bartholdy, Boris, Garrett-Bakelman, Francine, Mayer, Jillian, Barreyro, Laura, Pandolfi, Ashley, Todorova, Tihomira I., Okoye-Okafor, Ujunwa C., Stanley, Robert F., Bhagat, Tushar D., Verma, Amit, Figueroa, Maria E., Melnick, Ari, Roth, Michael, Steidl, Ulrich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633104/
https://www.ncbi.nlm.nih.gov/pubmed/23563689
http://dx.doi.org/10.1038/ni.2572
Descripción
Sumario:How hematopoietic stem cells coordinate the regulation of opposing cellular mechanisms like self-renewal and differentiation commitment remains unclear. Here, we identified the transcription factor and chromatin remodeler Satb1 as a critical regulator of the hematopoietic stem cell (HSC) fate. HSCs lacking Satb1 displayed defective self-renewal, less quiescence and accelerated lineage commitment, resulting in progressive depletion of functional HSCs. Increased commitment was caused by reduced symmetric self-renewal and increased symmetric differentiation divisions of Satb1-deficient HSCs. Satb1 simultaneously repressed gene sets involved in HSC activation and cellular polarity, including Numb and Myc, two key factors for stem cell fate specification. Thus, Satb1 is a regulator that promotes HSC quiescence and represses lineage commitment.

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