MafB restricts M-CSF-dependent myeloid commitment divisions of hematopoietic stem cells.

Abstract : While hematopoietic stem cell (HSC) self-renewal is well studied, it remains unknown whether distinct control mechanisms enable HSC divisions that generate progeny cells with specific lineage bias. Here, we report that the monocytic transcription factor MafB specifically restricts the ability of M-CSF to instruct myeloid commitment divisions in HSCs. MafB deficiency specifically enhanced sensitivity to M-CSF and caused activation of the myeloid master-regulator PU.1 in HSCs in vivo. Single-cell analysis revealed that reduced MafB levels enabled M-CSF to instruct divisions producing asymmetric daughter pairs with one PU.1(+) cell. As a consequence, MafB(-/-) HSCs showed a PU.1 and M-CSF receptor-dependent competitive repopulation advantage specifically in the myelomonocytic, but not T lymphoid or erythroid, compartment. Lineage-biased repopulation advantage was progressive, maintained long term, and serially transplantable. Together, this indicates that an integrated transcription factor/cytokine circuit can control the rate of specific HSC commitment divisions without compromising other lineages or self-renewal.
Type de document :
Article dans une revue
Cell, Elsevier, 2009, 138 (2), pp.300-13. 〈10.1016/j.cell.2009.04.057〉
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Contributeur : Maité Peney <>
Soumis le : lundi 28 septembre 2009 - 12:49:02
Dernière modification le : jeudi 18 janvier 2018 - 02:30:59

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Sandrine Sarrazin, Noushine Mossadegh-Keller, Taro Fukao, Athar Aziz, Frederic Mourcin, et al.. MafB restricts M-CSF-dependent myeloid commitment divisions of hematopoietic stem cells.. Cell, Elsevier, 2009, 138 (2), pp.300-13. 〈10.1016/j.cell.2009.04.057〉. 〈inserm-00420157〉



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