2012年10月20日 讯 /生物谷BIOON/ --化疗杀死血细胞，也能够杀死癌细胞，因此经常伴随着致命的结果。如今，耶鲁大学干细胞研究人员鉴定出一种方法，他们希望这种方法有朝一日将有助于接受化疗治疗的癌症病人维持一种健康的血液供应。相关研究结果于10月18日刊登在Cell Reports期刊上。
在耶鲁大学干细胞中心与癌症中心遗传学助理教授Jun Lu的指导下，研究人员研究了血细胞如何再生。Lu对小片段被称作微RNA(microRNA, miR)的遗传物资在血液产生和血干细胞和祖细胞功能所发挥的作用特别感兴趣。这些血祖细胞有助于确定所产生的血细胞类型。化疗杀死这些类型的血祖细胞，使得血液再生很困难。尽管红细胞能够通过灌注被替换，但是白细胞和血小板经常不能很好地复原，这就使得癌症病人很容易遭受感染和出血。
利用一种新技术来同时分析活小鼠体内的大量miR，研究人员鉴定出几种miR参与血液形成。当他们让这几种miR中的miR-150失去功能时，他们发现小鼠能够更加有效地再生化疗所破坏的白细胞和血小板。缺乏这种这种miR的小鼠没有表现出不良的健康影响。相反地，携带活性miR-150 的小鼠很难再生新的血细胞。
Lu说，“我们希望发现这些参与血液形成的特异性miR将给我们提供方法来不仅帮助癌症病人在化疗中存活下来，而且也使得化疗更加有效。”(生物谷Bioon.com)
doi: 10.1016/j.celrep.2012.09.014
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An In Vivo Functional Screen Uncovers miR-150-Mediated Regulation of Hematopoietic Injury Response
Brian D. Adams, Shangqin Guo, Haitao Bai, Yanwen Guo, Cynthia M. Megyola, Jijun Cheng, Kartoosh Heydari, Changchun Xiao, E. Premkumar Reddy, Jun Lu
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.
