2012年10月30日 訊 /生物谷BIOON/ --近日,,以色列,美國和其他國家研究人員共同合作在再生醫(yī)學領域中獲得了突破性研究進展,,研究結合首次概述與心臟和面部肌肉出生缺陷相關的基因調控,。
約1%的人有先天性心臟缺陷,這項新研究將便于科學家們利用患者自身的干細胞來修復缺陷,。這項研究結果在線發(fā)表在PNAS雜志上,。俄勒岡州立大學藥學院副教授Chrissa Kioussi說:隨著再生醫(yī)學和發(fā)育生物學的發(fā)展,我們不再需要制造人類胚胎干細胞來治療疾病,。
Kioussi說:來自患者的干細胞可以變成任何需要的細胞類型,。關鍵是了解干細胞演變過程總確切的監(jiān)管過程。一旦我們了解這些基因控制機制和足夠細節(jié),,我們不但能把干細胞轉化為皮膚細胞,,也能將這種干細胞分化為病人恢復所需要的細胞類型。
在這項研究中,,研究人員發(fā)現了4個具體的“轉錄因子”基因控制心臟和頭部肌肉形成過程,。在這個過程中,基因有缺陷時,,其結果可能是人死亡或巨大傷害性的如唇顎裂,,面部畸形和有缺陷的心臟瓣膜。
Kioussi說:人類基因組中有大約20,000個基因,,但只有2000多種轉錄因子基因,。這些轉錄因子基因控制遺傳機制??茖W家們發(fā)現,,這些轉錄因子不會單獨在哺乳動物細胞中發(fā)揮作用, 它們至少有兩個或三個一起穩(wěn)定組合共同發(fā)揮作用,。在這項再生醫(yī)學研究工作中,,研究人員關心細胞分化所有步驟。如果能知道所有的步驟,,就能機體缺陷出錯在哪里,,可以找出解決它的方法,。(生物谷:Bioon.com)
doi:10.1073/pnas.1208690109
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Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis
Itamar Harela, Yoshiro Maezawab, Roi Avrahama, Ariel Rinona, Hsiao-Yen Mac, et al.
The search for developmental mechanisms driving vertebrate organogenesis has paved the way toward a deeper understanding of birth defects. During embryogenesis, parts of the heart and craniofacial muscles arise from pharyngeal mesoderm (PM) progenitors. Here, we reveal a hierarchical regulatory network of a set of transcription factors expressed in the PM that initiates heart and craniofacial organogenesis. Genetic perturbation of this network in mice resulted in heart and craniofacial muscle defects, revealing robust cross-regulation between its members. We identified Lhx2 as a previously undescribed player during cardiac and pharyngeal muscle development. Lhx2 and Tcf21 genetically interact with Tbx1, the major determinant in the etiology of DiGeorge/velo-cardio-facial/22q11.2 deletion syndrome. Furthermore, knockout of these genes in the mouse recapitulates specific cardiac features of this syndrome. We suggest that PM-derived cardiogenesis and myogenesis are network properties rather than properties specific to individual PM members. These findings shed new light on the developmental underpinnings of congenital defects.