来自美国康奈尔大学霍华德休斯医学研究所的Shahin Rafii实验室发现通过ETS因子和TGFβ的抑制作用成熟的羊水细胞经过有效直接的重排作用形成上皮细胞,本篇文章刊登在最新一期《CELL》杂志上。

-2012年10月26日《细胞》


中文翻译


【题目】成熟的羊水细胞经过有效直接的重排作用形成上皮细胞

【译文】ETSz转录因子ETV2,FLI1和ERG1促使多潜能干细胞形成被诱导的血管内皮细胞(iVECs)。然而,iVECs是不稳定且趋向于形成非血管性的细胞。我们证明了人类侏儒c-Kit−定型谱系的羊水细胞(ACs)可以通过可塑阶段在无转变的情况下重排形成血管内皮细胞(rAC-VECs)。在ACs中短暂的ETV2的表达形成早期的rAC-VECs,但是与FLI1/ERG1的共表达赋予了rAC-VECs与上皮细胞(ECs)配对的血管成分和形态学。TGFβ短暂的抑制作用使得VEGFR2信号通路发挥作用,从而使得ACs向rAC-VECs扩张。全基因组转录分析表明rAC-VECs与成年的ECs很相似,在ECs中血管特异性的基因被表达而非血管的基因被沉默。从功能上来说,rAC-VECs在基质胶制备的血管模型和再生的肝脏中形成稳定的脉管系统。因此,短暂的ETV2的表达及伴有组成型ERG1/FLI1共表达重编程的TGFβ抑制作用可以使得ACs成熟以形成具有临床分级潜力的持久rAC-VECs。HLA型rAC-VECs的蓄积建立了一个血管清单来应对各种系统紊乱。

英文原稿


[Title]Efficient Direct Reprogramming of Mature Amniotic Cells into Endothelial Cells by ETS Factors and TGFβ Suppression

[Authors]Michael Ginsberg, Daylon James, Bi-Sen Ding, Daniel Nolan, Fuqiang Geng, Jason M. Butler, William Schachterle, Venkat R. Pulijaal, Susan Mathew, Stephen T. Chasen, Jenny Xiang, Zev Rosenwaks, Koji Shido, Olivier Elemento, Sina Y. Rabbany, Shahin Rafii

[Abstract]ETS transcription factors ETV2, FLI1, and ERG1 specify pluripotent stem cells into induced vascular endothelial cells (iVECs). However, iVECs are unstable and drift toward nonvascular cells. We show that human midgestation c-Kit− lineage-committed amniotic cells (ACs) can be reprogrammed into vascular endothelial cells (rAC-VECs) without transitioning through a pluripotent state. Transient ETV2 expression in ACs generates immature rAC-VECs, whereas coexpression with FLI1/ERG1 endows rAC-VECs with a vascular repertoire and morphology matching mature endothelial cells (ECs). Brief TGFβ-inhibition functionalizes VEGFR2 signaling, augmenting specification of ACs into rAC-VECs. Genome-wide transcriptional analyses showed that rAC-VECs are similar to adult ECs in which vascular-specific genes are expressed and nonvascular genes are silenced. Functionally, rAC-VECs form stable vasculature in Matrigel plugs and regenerating livers. Therefore, short-term ETV2 expression and TGFβ inhibition with constitutive ERG1/FLI1 coexpression reprogram mature ACs into durable rAC-VECs with clinical-scale expansion potential. Banking of HLA-typed rAC-VECs establishes a vascular inventory for treatment of diverse disorders.

原文地址

http://www.cell.com/abstract/S0092-8674(12)01178-6

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