Cell Reports
Volume 2, Issue 4, 25 October 2012, Pages 1048-1060
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An In Vivo Functional Screen Uncovers miR-150-Mediated Regulation of Hematopoietic Injury Response

https://doi.org/10.1016/j.celrep.2012.09.014Get rights and content
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Summary

Hematopoietic stem and progenitor cells are often undesired targets of chemotherapies, leading to hematopoietic suppression requiring careful clinical management. Whether microRNAs control hematopoietic injury response is largely unknown. We report an in vivo gain-of-function screen and the identification of miR-150 as an inhibitor of hematopoietic recovery upon 5-fluorouracil-induced injury. Utilizing a bone marrow transplant model with a barcoded microRNA library, we screened for barcode abundance in peripheral blood of recipient mice before and after 5-fluorouracil treatment. Overexpression of screen-candidate miR-150 resulted in significantly slowed recovery rates across major blood lineages, with associated impairment of bone marrow clonogenic potential. Conversely, platelets and myeloid cells from miR-150 null marrow recovered faster after 5-fluorouracil treatment. Heterozygous knockout of c-myb, a conserved target of miR-150, partially phenocopied miR-150-forced expression. Our data highlight the role of microRNAs in controlling hematopoietic injury response and demonstrate the power of in vivo functional screens for studying microRNAs in normal tissue physiology.

Highlights

► In vivo miRNA screen identified regulators of hematopoietic injury response ► miR-150 expression inhibits hematopoietic recovery across multiple lineages ► Upon injury, miR-150 null cells contribute faster to peripheral blood recovery ► Partial loss of the miR-150 target c-myb delays hematopoietic recovery

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