TitleSatb1 regulates the self-renewal of hematopoietic stem cells by promoting quiescence and repressing differentiation commitment.
Publication TypeJournal Article
Year of Publication2013
AuthorsWill, 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, and Steidl Ulrich
JournalNat Immunol
Date Published2013 May
KeywordsAnimals, Cell Differentiation, Cell Lineage, Cell Polarity, Cell Survival, Cells, Cultured, Chromatin Assembly and Disassembly, Gene Expression Regulation, Developmental, Hematopoietic Stem Cells, Matrix Attachment Region Binding Proteins, Membrane Proteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Nerve Tissue Proteins, Proto-Oncogene Proteins c-myc

<p>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.</p>

Alternate JournalNat Immunol
PubMed ID23563689
PubMed Central IDPMC3633104
Grant ListF31CA162770 / CA / NCI NIH HHS / United States
K08 CA169055 / CA / NCI NIH HHS / United States
R01 CA166429 / CA / NCI NIH HHS / United States
F31 CA162770 / CA / NCI NIH HHS / United States
R00CA131503 / CA / NCI NIH HHS / United States
F30HL117545 / HL / NHLBI NIH HHS / United States
F30 HL117545 / HL / NHLBI NIH HHS / United States
(1K08CA169055-01 / CA / NCI NIH HHS / United States
T32 GM007288 / GM / NIGMS NIH HHS / United States
R00 CA131503 / CA / NCI NIH HHS / United States