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1.95单职业传奇-研究发现靶向OLIG2有助于治疗唐氏综合症

作者:超变单职业_变态单职业_超变单职业传奇_就来新开单职业传奇发布网2019-07-11 19:33类型:刚开一秒传奇Sf 已有124人围观

罗格斯大学江鹏课题组宣布他们发现了OLIG2在基于ipsc的人源嵌合的唐氏综合征小鼠模型中驱动异常的神经发育表型,靶向OLIG2有助于治疗唐氏综合症。该项研究发表在2019年6月4日出版的《Cell Stem Cell》上。

课题组发现,人类诱导的多能干细胞(hipscs)源于唐氏综合症(DS)患者生产过剩的OLIG2+腹侧前脑神经祖细胞。因此,DS hiPSC衍生的脑类器官过度产生GABAergic中间神经元的特定亚类,并导致神经元嵌合体小鼠的识别记忆受损。DS细胞中OLIG2表达的增加直接上调了决定转录因子的神经元间谱系。shRNA介导的OLIG2敲除在很大程度上逆转了DS神经祖细胞早期的异常基因表达,在新开传奇网站的游戏中,降低DS类器官和嵌合体小鼠大脑中的神经元间产生,改善DS嵌合体小鼠的行为缺陷。因此,Olig2表达的改变可能是DS患者神经发育异常和认知缺陷的基础。

据悉,唐氏综合症(DS)是一种常见的神经发育障碍,DS患者的认知缺陷可能是由兴奋性和抑制性神经传递失衡引起的。了解这种失衡背后的机制可能为治疗干预提供机会。

附:英文原文

Title: OLIG2 Drives Abnormal Neurodevelopmental Phenotypes in Human iPSC-Based Organoid and Chimeric Mouse Models of Down Syndrome

Author: Ranjie Xu, Andrew T. Brawner, Shenglan Li, Jing-Jing Liu, Hyosung Kim, Haipeng Xue, Zhiping P. Pang, Woo-Yang Kim, Ronald P. Hart, Ying Liu, Peng Jiang

Issue&Volume: Jun 06, 2019 Volume 24Issue 6

Abstract: Down syndrome (DS) is a common neurodevelopmental disorder, and cognitive defects in DS patients may arise from imbalances in excitatory and inhibitory neurotransmission. Understanding the mechanisms underlying such imbalances may provide opportunities for therapeutic intervention. Here, we show that human induced pluripotent stem cells (hiPSCs) derived from DS patients overproduce OLIG2 + ventral forebrain neural progenitors. As a result, DS hiPSC-derived cerebral organoids excessively produce specific subclasses of GABAergic interneurons and cause impaired recognition memory in neuronal chimeric mice. Increased OLIG2 expression in DS cells directly upregulates interneuron lineage-determining transcription factors. shRNA-mediated knockdown of OLIG2 largely reverses abnormal gene expression in early-stage DS neural progenitors, reduces interneuron production in DS organoids and chimeric mouse brains, and improves behavioral deficits in DS chimeric mice. Thus, altered OLIG2 expression may underlie neurodevelopmental abnormalities and cognitive defects in DS patients.

DOI: https://doi.org/10.1016/j.stem.2019.04.014

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30163-8

期刊信息

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,在超变传奇私服里面,最新if:21.464
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx

-Jun 06, 2019 Volume 24Issue 6

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