近日來(lái)自澳大利亞墨爾本沃爾特-伊萊扎霍爾醫(yī)學(xué)研究院（Walter and Eliza Hall Institute）的一項(xiàng)最新研究表明成熟血細(xì)胞能夠與親代干細(xì)胞“溝通”,，并影響其行為,。機(jī)體內(nèi)血細(xì)胞反饋環(huán)的發(fā)現(xiàn)為研究干細(xì)胞機(jī)能紊亂引起的疾病及開發(fā)新的治療方法開辟了新道路。研究結(jié)果發(fā)表在11月29日的PNAS上,，揭示了從前未知的血細(xì)胞間的相互關(guān)系,。
來(lái)自分子醫(yī)學(xué)系的Carolyn de Graaf博士和Doug Hilton教授以及來(lái)自癌癥和血液病學(xué)系的Warren Alexander領(lǐng)導(dǎo)了該項(xiàng)研究,。
“我們知道血液干細(xì)胞可生成所有類型的成熟血細(xì)胞?？茖W(xué)家們一直猜想是外部的因素調(diào)控了血細(xì)胞生成,，并且兩個(gè)群體相互孤立存在，”Hilton教授說(shuō)：“然而新研究表明成熟細(xì)胞事實(shí)上可反作用于干細(xì)胞,，改變其基因表達(dá)以及影響它們的行為,。”
研究人員發(fā)現(xiàn)血細(xì)胞異常可引起反饋環(huán)失調(diào),，進(jìn)而對(duì)血液干細(xì)胞產(chǎn)生影響,。研究人員在動(dòng)物模型中研究了一種抑制血小板生成的轉(zhuǎn)錄因子Myb，在檢測(cè)Myb缺失對(duì)細(xì)胞的影響時(shí)發(fā)現(xiàn)了這一現(xiàn)象,。de Graaf博士說(shuō)Myb基因缺失可導(dǎo)致動(dòng)物血液中產(chǎn)生高水平的血小板,，從而引起維持干細(xì)胞的信號(hào)途徑發(fā)生改變。
“當(dāng)信號(hào)途徑發(fā)生改變時(shí),，這些干細(xì)胞不再維持在一種‘靜止?fàn)顟B(tài)’,，而是在不斷地循環(huán),，生成成熟干細(xì)胞，”de Graaf博士說(shuō)：“最終干細(xì)胞會(huì)耗盡,，由于缺乏足夠的干細(xì)胞生成新的紅細(xì)胞和白細(xì)胞,，從而導(dǎo)致機(jī)體血液疾病發(fā)生。”
此外,，研究人員還利用新一代的基因組技術(shù)鑒定了缺陷信號(hào)所致的血液干細(xì)胞中的基因標(biāo)記。這些基因標(biāo)記有可能在將來(lái)用于診斷和輔助疾病治療,。
“如果我們能夠了解這些基因在干細(xì)胞維持和血細(xì)胞生成中的重要作用,，我們就能夠找到一些新途徑提高移植技術(shù)和血液疾病的治療，”de Graaf博士說(shuō),。
Hilton教授認(rèn)為新發(fā)現(xiàn)將使那些干細(xì)胞衰竭的患者受益,。“我們所要做的事情就是確定這些干細(xì)胞的衰竭是否是由于成熟血細(xì)胞和干細(xì)胞之間的錯(cuò)誤溝通所致，這些發(fā)現(xiàn)將有可能促使我們找到新的途徑治療這些疾病,，”Hilton教授說(shuō),。（生物谷Bioon.com）
生物谷推薦原文出處：
PNAS | doi: 10.1073/pnas.1016166108
Regulation of hematopoietic stem cells by their mature progeny
Carolyn A. de Graafa,b, Maria Kauppic, Tracey Baldwina, Craig D. Hylandc, Donald Metcalfc,1, Tracy A. Willsona, Marina R. Carpinellia, Gordon K. Smythd,e, Warren S. Alexanderc,b,2, and Douglas J. Hiltona,b,1,2
+ Author Affiliations
aMolecular Medicine Division,
cCancer and Haematology Division, and
dBioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; and
Departments of bMedical Biology and
eMathematics and Statistics, University of Melbourne, Parkville, Victoria 3010, Australia
Contributed by Donald Metcalf, October 27, 2010 (sent for review August 23, 2010)
?2W.S.A. and D.J.H. contributed equally to this work.
Abstract
Thrombopoietin (TPO), acting through its receptor Mpl, has two major physiological roles: ensuring production of sufficient platelets via stimulation of megakaryocyte production and maintaining hematopoietic stem cell (HSC) quiescence. Mpl also controls circulating TPO concentration via receptor-mediated internalization and degradation. Here, we demonstrate that the megakaryocytosis and increased platelet mass in mice with mutations in the Myb or p300 genes causes reduced circulating TPO concentration and TPO starvation of the stem-cell compartment, which is exacerbated because these cells additionally exhibit impaired responsiveness to TPO. HSCs from MybPlt4/Plt4 mice show altered expression of TPO-responsive genes and, like HSCs from Tpo and Mpl mutant mice, exhibit increased cycling and a decline in the number of HSCs with age. These studies suggest that disorders of platelet number can have profound effects on the HSC compartment via effects on the feedback regulation of circulating TPO concentration.
