title: Satb1 regulates the self-renewal of hematopoietic stem cells by promoting quiescence and repressing differentiation commitment.
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.
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Britta
authors.initials: B
authors.lastname: Will
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Vogler
authors.forename: Boris
authors.initials: B
authors.lastname: Bartholdy
authors.forename: Francine
authors.initials: F
authors.lastname: Garrett-Bakelman
authors.forename: Jillian
authors.initials: J
authors.lastname: Mayer
authors.forename: Laura
authors.initials: L
authors.lastname: Barreyro
authors.forename: Ashley
authors.initials: A
authors.lastname: Pandolfi
authors.forename: Tihomira I
authors.initials: TI
authors.lastname: Todorova
authors.forename: Ujunwa C
authors.initials: UC
authors.lastname: Okoye-Okafor
authors.forename: Robert F
authors.initials: RF
authors.lastname: Stanley
authors.forename: Tushar D
authors.initials: TD
authors.lastname: Bhagat
authors.forename: Amit
authors.initials: A
authors.lastname: Verma
authors.forename: Maria E
authors.initials: ME
authors.lastname: Figueroa
authors.forename: Ari
authors.initials: A
authors.lastname: Melnick
authors.forename: Michael
authors.initials: M
authors.lastname: Roth
authors.forename: Ulrich
authors.initials: U
authors.lastname: Steidl
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism
chemical_list: D036961:Matrix Attachment Region Binding Proteins; D008565:Membrane Proteins; C489428:Myc protein, mouse; D009419:Nerve Tissue Proteins; C106293:Numb protein, mouse; D016271:Proto-Oncogene Proteins c-myc; C469541:Satb1 protein, mouse
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