近日,，軍事醫(yī)學(xué)科學(xué)院附屬醫(yī)院（解放軍307醫(yī)院）劉兵課題組和軍事醫(yī)學(xué)科學(xué)院生物工程研究所楊曉課題組通過合作,，發(fā)現(xiàn)小鼠胚胎頭部是造血干細(xì)胞發(fā)育的新位點(diǎn)。相關(guān)研究成果于11月2日以研究論文形式發(fā)表于國際期刊《細(xì)胞—干細(xì)胞》,，論文第一作者為博士生李專和副研究員蘭雨,。
造血干細(xì)胞的胚胎起源是干細(xì)胞生物學(xué)領(lǐng)域的研究熱點(diǎn)。近20年來,，主流學(xué)術(shù)觀點(diǎn)認(rèn)為：胚胎尾側(cè)的主動(dòng)脈—性腺—中腎區(qū)（AGM區(qū)）是小鼠胚內(nèi)唯一產(chǎn)生造血干細(xì)胞的區(qū)域,。盡管有證據(jù)提示頭側(cè)造血活性的存在，但該假說卻一直缺乏系統(tǒng)性研究,。
為深入分析胚胎頭部的造血活動(dòng),，課題組成員進(jìn)行了系統(tǒng)的體內(nèi)和體外造血活性檢測(cè)。令人驚喜的是,，通過長(zhǎng)達(dá)一年的移植實(shí)驗(yàn),，研究結(jié)果顯示，小鼠胚胎10.5～11.5天的頭部細(xì)胞與AGM區(qū)細(xì)胞相似,，能長(zhǎng)期,、高效重建經(jīng)致死劑量照射小鼠的整個(gè)造血系統(tǒng)。這表明,，其具有標(biāo)準(zhǔn)的造血干細(xì)胞潛能,，早于其在胚胎循環(huán)血中的出現(xiàn)。
進(jìn)一步的形態(tài)學(xué)分析表明,，胚胎腦部血管腔中存在“出芽”的血細(xì)胞簇,，提示腦血管內(nèi)皮細(xì)胞有生血的活動(dòng)。繼而,，通過純化的內(nèi)皮細(xì)胞功能分析以及可誘導(dǎo)的內(nèi)皮細(xì)胞命運(yùn)示蹤等手段,，研究人員確認(rèn)腦血管內(nèi)皮細(xì)胞具有產(chǎn)生造血細(xì)胞的能力。
更重要的是,，利用一種獨(dú)特的腦血管內(nèi)皮細(xì)胞特異性Cre重組酶轉(zhuǎn)基因小鼠,，研究人員發(fā)現(xiàn)，腦血管內(nèi)皮細(xì)胞不僅可以原位產(chǎn)生造血細(xì)胞,，還貢獻(xiàn)了成體的造血干細(xì)胞及各類成熟造血細(xì)胞。（生物谷Bioon.com）
doi:10.1016/j.stem.2012.07.004
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Mouse Embryonic Head as a Site for Hematopoietic Stem Cell Development
Zhuan Li, Yu Lan, Wenyan He, Dongbo Chen, Jun Wang, Fan Zhou, Yu Wang, Huayan Sun, Xianda Chen, Chunhong Xu, Sha Li, Yakun Pang, Guangzhou Zhang, Liping Yang, Lingling Zhu, Ming Fan, Aijia Shang, Zhenyu Ju, Lingfei Luo, Yuqiang Ding, Wei Guo, Weiping Yuan, Xiao Yang, Bing Liu
In the mouse embryo, the aorta-gonad-mesonephros (AGM) region is considered to be the sole location for intraembryonic emergence of hematopoietic stem cells (HSCs). Here we report that, in parallel to the AGM region, the E10.5–E11.5 mouse head harbors bona fide HSCs, as defined by long-term, high-level, multilineage reconstitution and self-renewal capacity in adult recipients, before HSCs enter the circulation. The presence of hemogenesis in the midgestation head is indicated by the appearance of intravascular cluster cells and the blood-forming capacity of a sorted endothelial cell population. In addition, lineage tracing via an inducible VE-cadherin-Cre transgene demonstrates the hemogenic capacity of head endothelium. Most importantly, a spatially restricted lineage labeling system reveals the physiological contribution of cerebrovascular endothelium to postnatal HSCs and multilineage hematopoiesis. We conclude that the mouse embryonic head is a previously unappreciated site for HSC emergence within the developing embryo.
