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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation / genetics
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Cell Lineage / genetics
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Cell Polarity / genetics
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Cell Survival / genetics
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Cells, Cultured
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Chromatin Assembly and Disassembly / genetics
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Gene Expression Regulation, Developmental / genetics
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Hematopoietic Stem Cells / physiology*
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Matrix Attachment Region Binding Proteins / genetics
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Matrix Attachment Region Binding Proteins / metabolism*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / metabolism
Substances
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Matrix Attachment Region Binding Proteins
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Membrane Proteins
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Myc protein, mouse
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Nerve Tissue Proteins
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Numb protein, mouse
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Proto-Oncogene Proteins c-myc
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Satb1 protein, mouse
Associated data
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GEO/GSE44107
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GEO/GSE44304