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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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
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author 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
author_facet 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
author_sort Will, Britta
collection PubMed
description 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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spelling pubmed-36331042013-11-01 Satb1 regulates hematopoietic stem cell self-renewal by promoting quiescence and repressing differentiation commitment 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 Nat Immunol Article 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. 2013-04-07 2013-05 /pmc/articles/PMC3633104/ /pubmed/23563689 http://dx.doi.org/10.1038/ni.2572 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
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
Satb1 regulates hematopoietic stem cell self-renewal by promoting quiescence and repressing differentiation commitment
title Satb1 regulates hematopoietic stem cell self-renewal by promoting quiescence and repressing differentiation commitment
title_full Satb1 regulates hematopoietic stem cell self-renewal by promoting quiescence and repressing differentiation commitment
title_fullStr Satb1 regulates hematopoietic stem cell self-renewal by promoting quiescence and repressing differentiation commitment
title_full_unstemmed Satb1 regulates hematopoietic stem cell self-renewal by promoting quiescence and repressing differentiation commitment
title_short Satb1 regulates hematopoietic stem cell self-renewal by promoting quiescence and repressing differentiation commitment
title_sort satb1 regulates hematopoietic stem cell self-renewal by promoting quiescence and repressing differentiation commitment
topic Article
url 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
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