Satb1 Regulates the Self-renewal of Hematopoietic Stem Cells by Promoting Quiescence and Repressing Differentiation Commitment

Overview

Journal Nat Immunol

Date 2013 Apr 9

PMID 23563689

Citations 67

Authors

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

Affiliations

Soon will be listed here.

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.

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