造血干細(xì)胞是血液組織中的一部分,當(dāng)它們被移植到受者時(shí),,能夠產(chǎn)生血液組織中的全部細(xì)胞,。來自IMIM(Hospital del Mar Medical Research Institute)的研究人員揭示出一種被稱作β-連環(huán)蛋白(β-catenin)的蛋白在產(chǎn)生造血干細(xì)胞中所發(fā)揮的功能。造血干細(xì)胞被用于移植來對抗不同類型的白血病,。這些研究結(jié)果將為人們在實(shí)驗(yàn)室中生產(chǎn)這些干細(xì)胞打開大門,。在未來,這也將讓沒有合適供者的病人能夠從這項(xiàng)發(fā)現(xiàn)中獲利,。2012年7月16日,,相關(guān)研究結(jié)果在線發(fā)表在Journal of Experimental Medicine期刊上。
在這項(xiàng)研究中,,研究人員分析了一些胚胎細(xì)胞內(nèi)部產(chǎn)生的一系列分子反應(yīng),,其中這些胚胎細(xì)胞在產(chǎn)生造血干細(xì)胞中發(fā)揮著作用。論文通訊作者Anna Bigas博士說,,“我們的研究有助于揭示讓只在胚胎中發(fā)現(xiàn)的一種前體細(xì)胞變成造血干細(xì)胞的秘密,。如果要這種前體細(xì)胞變成造血干細(xì)胞,那么β-連環(huán)蛋白必必須被激活一段時(shí)間同時(shí)維持一種特定的劑量,。”
這種蛋白也在產(chǎn)生和維持一些類型的白血病中發(fā)揮著基礎(chǔ)性的作用,。在正常干細(xì)胞和白血病干細(xì)胞之間存在的這種類似性表明調(diào)節(jié)這種細(xì)胞群體的分子途徑是一樣的。因此,,這項(xiàng)研究將有助于人們理解這些疾病的起源,。(生物谷:Bioon.com)
本文編譯自Key function of protein discovered for obtaining blood stem cells as source for transplants
doi: 10.1084/jem.20120225
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Hematopoietic stem cell development requires transient Wnt/β-catenin activity
Cristina Ruiz-Herguido1, Jordi Guiu1, Teresa D'Altri1, Julia Inglés-Esteve1, Elaine Dzierzak2, Lluis Espinosa1, and Anna Bigas
Understanding how hematopoietic stem cells (HSCs) are generated and the signals that control this process is a crucial issue for regenerative medicine applications that require in vitro production of HSC. HSCs emerge during embryonic life from an endothelial-like cell population that resides in the aorta-gonad-mesonephros (AGM) region. We show here that β-catenin is nuclear and active in few endothelial nonhematopoietic cells closely associated with the emerging hematopoietic clusters of the embryonic aorta during mouse development. Importantly, Wnt/β-catenin activity is transiently required in the AGM to generate long-term HSCs and to produce hematopoietic cells in vitro from AGM endothelial precursors. Genetic deletion of β-catenin from the embryonic endothelium stage (using VE-cadherin–Cre recombinase), but not from embryonic hematopoietic cells (using Vav1-Cre), precludes progression of mutant cells toward the hematopoietic lineage; however, these mutant cells still contribute to the adult endothelium. Together, those findings indicate that Wnt/β-catenin activity is needed for the emergence but not the maintenance of HSCs in mouse embryos.