2016 Fiscal Year Final Research Report
A Bach2-Cebp gene regulatory network for the commitment of multipotent hematopoietic progenitors
| Project/Area Number |
15K18998
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General medical chemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Keywords | 血球分化 / 転写因子 / 遺伝子発現制御 / コミットメント |
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| Outline of Final Research Achievements |
Hematopoietic stem cells and multipotent progenitors (MPPs) commitment can be tuned in response to an infection so that their differentiation is biased toward myeloid cells. Here we find that Bach2, which inhibits myeloid differentiation in common lymphoid progenitors, represses a cohort of myeloid genes and activates those linked to lymphoid function. Bach2 repressed both Cebpb and its target Csf1r, encoding C/EBPβ and macrophage colony-stimulating factor receptor (M-CSFr), respectively, whereas C/EBPβ repressed Bach2 and activated Csf1r. Bach2 and C/EBPβ further bound to overlapping regulatory regions at their myeloid target genes.Lipopolysaccharide reduced the expression of Bach2, resulting in enhanced myeloid differentiation. The Bach2-C/EBPβ GRN pathway thus tunes MPP commitment to myeloid and lymphoid lineages under both normal conditions and after infection.
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| Free Research Field |
免疫学
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