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

Sarrazin, S, Mossadegh-Keller, N, Fukao, T, Aziz, A, Mourcin, F, Vanhille, L, Kelly Modis, L, Kastner, P, Chan, S, Duprez, E, Otto, C and Sieweke, MH 2009, 'MafB restricts M-CSF-Dependent myeloid commitment divisions of hematopoietic stem cells' , Cell, 138 (2) , pp. 300-313.

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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.

Item Type: Article
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Journal or Publication Title: Cell
Publisher: Elsevier
Refereed: Yes
ISSN: 0092-8674
Related URLs:
Funders: Funder not known
Depositing User: H Kenna
Date Deposited: 12 Sep 2014 15:20
Last Modified: 12 Sep 2014 15:20
URI: http://usir.salford.ac.uk/id/eprint/32302

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