کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2036748 1072280 2009 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
MafB Restricts M-CSF-Dependent Myeloid Commitment Divisions of Hematopoietic Stem Cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوشیمی، ژنتیک و زیست شناسی مولکولی (عمومی)
پیش نمایش صفحه اول مقاله
MafB Restricts M-CSF-Dependent Myeloid Commitment Divisions of Hematopoietic Stem Cells
چکیده انگلیسی

SummaryWhile 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 138, Issue 2, 23 July 2009, Pages 300–313
نویسندگان
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