2012年10月20日 訊 /生物谷BIOON/ --化療殺死血細胞,，也能夠殺死癌細胞,，因此經(jīng)常伴隨著致命的結(jié)果。如今,，耶魯大學干細胞研究人員鑒定出一種方法,，他們希望這種方法有朝一日將有助于接受化療治療的癌癥病人維持一種健康的血液供應。相關研究結(jié)果于10月18日刊登在Cell Reports期刊上,。
在耶魯大學干細胞中心與癌癥中心遺傳學助理教授Jun Lu的指導下,，研究人員研究了血細胞如何再生。Lu對小片段被稱作微RNA(microRNA, miR)的遺傳物資在血液產(chǎn)生和血干細胞和祖細胞功能所發(fā)揮的作用特別感興趣,。這些血祖細胞有助于確定所產(chǎn)生的血細胞類型,。化療殺死這些類型的血祖細胞,，使得血液再生很困難,。盡管紅細胞能夠通過灌注被替換，但是白細胞和血小板經(jīng)常不能很好地復原,，這就使得癌癥病人很容易遭受感染和出血,。
利用一種新技術來同時分析活小鼠體內(nèi)的大量miR，研究人員鑒定出幾種miR參與血液形成,。當他們讓這幾種miR中的miR-150失去功能時,，他們發(fā)現(xiàn)小鼠能夠更加有效地再生化療所破壞的白細胞和血小板。缺乏這種這種miR的小鼠沒有表現(xiàn)出不良的健康影響,。相反地,，攜帶活性miR-150 的小鼠很難再生新的血細胞。
Lu說,，“我們希望發(fā)現(xiàn)這些參與血液形成的特異性miR將給我們提供方法來不僅幫助癌癥病人在化療中存活下來,，而且也使得化療更加有效。”(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.
