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PMID: 23563689 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature immunology ·Vol. 14 ·No. 5 ·2013-05-00 ·Pages 437-45

Will B, Vogler TO, Bartholdy B, Garrett-Bakelman F, Mayer J, Barreyro L, Pandolfi A, Todorova TI, Okoye-Okafor UC, Stanley RF, Bhagat TD, Verma A, Figueroa ME, Melnick A, Roth M, Steidl U

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.

MeSH Terms
Animals Cell Differentiation/genetics Cell Lineage/genetics Cell Polarity/genetics Cell Survival/genetics Cells, Cultured Chromatin Assembly and Disassembly/genetics Gene Expression Regulation, Developmental/genetics Hematopoietic Stem Cells/physiology Matrix Attachment Region Binding Proteins/genetics,metabolism Membrane Proteins/genetics,metabolism Mice Mice, Inbred C57BL Mice, Knockout Nerve Tissue Proteins/genetics,metabolism Proto-Oncogene Proteins c-myc/genetics,metabolism
Chemicals
Matrix Attachment Region Binding Proteins Membrane Proteins Myc protein, mouse Nerve Tissue Proteins Numb protein, mouse Proto-Oncogene Proteins c-myc Satb1 protein, mouse
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Will Britta
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, USA.
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
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.2572
Published
2013-05-00
Epub
2013-00-07
Pages
437-45
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC3633104
Subset
IM
Grants
NCI NIH HHS · F31CA162770 · United States
NCI NIH HHS · K08 CA169055 · United States
NCI NIH HHS · R01 CA166429 · United States
NCI NIH HHS · F31 CA162770 · United States
NCI NIH HHS · R00CA131503 · United States
NHLBI NIH HHS · F30HL117545 · United States
NHLBI NIH HHS · F30 HL117545 · United States
NCI NIH HHS · (1K08CA169055-01 · United States
NIGMS NIH HHS · T32 GM007288 · United States
NCI NIH HHS · R00 CA131503 · United States
Databases
GEO
GSE44107, GSE44304
External Links
PubMed source DOI: 10.1038/ni.2572 PMC Full Text View journal details
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