賓夕法尼亞大學(xué)醫(yī)學(xué)院發(fā)育干細(xì)胞與再生生物學(xué)系教授Nancy A. Speck近期在在最新一期的Nature雜志發(fā)表干細(xì)胞轉(zhuǎn)錄研究新成果，該成果揭示了造血干細(xì)胞的分化調(diào)節(jié)因子Runx1的調(diào)節(jié)機(jī)制,。
Runx是CBFs的組成部分,，是其中的一個(gè)亞單位，CBFs有兩個(gè)亞結(jié)構(gòu)組成,，一個(gè)是結(jié)合DNA的區(qū)域,，一個(gè)是非DNA結(jié)合區(qū)域，Runx1就是結(jié)合DNA的區(qū)域,，主要分三種,，Runx1、Runx2和Runx3,。造血干細(xì)胞是成年人造血系統(tǒng)中的重要基礎(chǔ)細(xì)胞,，但是造血干細(xì)胞是如何發(fā)育分化的機(jī)制一直沒(méi)有破解。而Runx1是血管中造血干細(xì)胞發(fā)育的中樞轉(zhuǎn)錄控制因子,，有研究認(rèn)為造血干細(xì)胞來(lái)自于血管內(nèi)皮細(xì)胞,，先生成動(dòng)脈內(nèi)的細(xì)胞簇，接下來(lái)Runx1發(fā)揮調(diào)控作用,，促進(jìn)細(xì)胞簇轉(zhuǎn)化成造血干細(xì)胞。
在本研究中Nancy A. Speck教授的研究小組將脈管內(nèi)皮鈣粘蛋白陽(yáng)性的內(nèi)皮細(xì)胞中表達(dá)Runx1的基因敲除,，結(jié)果發(fā)現(xiàn)Runx1對(duì)動(dòng)脈內(nèi)細(xì)胞簇的生成具有關(guān)鍵的作用,，失去Runx1就無(wú)法生成造血干細(xì)胞。而另一個(gè)有趣的現(xiàn)象是,，Runx1的功能能被Vav1彌補(bǔ),，Vav1是首個(gè)造血干細(xì)胞的pan-Haematopoietic基因表達(dá)的蛋白產(chǎn)物。
這些研究成果表明,，Runx1是控制造血干細(xì)胞生成的關(guān)鍵控制因子,，不過(guò)，對(duì)能表達(dá)Vav的細(xì)胞來(lái)說(shuō),，Runx1卻并不是必須的,。Runx1是內(nèi)皮細(xì)胞-動(dòng)脈細(xì)胞簇-造血干細(xì)胞轉(zhuǎn)型過(guò)程中的過(guò)度調(diào)控因子。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature advance online publication 7 January 2009 | doi:10.1038/nature07619
Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter
Michael J. Chen1,2,4, Tomomasa Yokomizo3, Brandon M. Zeigler1, Elaine Dzierzak3 & Nancy A. Speck1,4
1 Department of Biochemistry,
2 Department of Genetics, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
3 Department of Cell Biology and Genetics, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands
4 Present address: Abramson Family Cancer Research Institute and Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Haematopoietic stem cells (HSCs) are the founder cells of the adult haematopoietic system, and thus knowledge of the molecular program directing their generation during development is important for regenerative haematopoietic strategies. Runx1 is a pivotal transcription factor required for HSC generation in the vascular regions of the mouse conceptus—the aorta, vitelline and umbilical arteries, yolk sac and placenta1, 2. It is thought that HSCs emerge from vascular endothelial cells through the formation of intra-arterial clusters3 and that Runx1 functions during the transition from 'haemogenic endothelium' to HSCs4, 5. Here we show by conditional deletion that Runx1 activity in vascular-endothelial-cadherin-positive endothelial cells is indeed essential for intra-arterial cluster, haematopoietic progenitor and HSC formation in mice. In contrast, Runx1 is not required in cells expressing Vav1, one of the first pan-haematopoietic genes expressed in HSCs. Collectively these data show that Runx1 function is essential in endothelial cells for haematopoietic progenitor and HSC formation from the vasculature, but its requirement ends once or before Vav is expressed.
