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绘制人类前脑发育模型中的染色质可及性动态图谱
作者:小柯机器人 发布时间:2020/1/29 16:39:38

美国斯坦福大学Sergiu P. Paca、William J. Greenleaf等研究人员合作绘制了人类前脑发育模型中的染色质可及性动态图谱。该项研究成果发表在2020年1月24日出版的《科学》上。

研究人员表示,前脑发育的特征是高度同步的细胞过程,如果受到干扰,会导致疾病。
 
为了绘制这些事件背后的调节活性图谱,研究人员生成了人类三维前脑类器官体中的可及性染色质图谱。为了捕获皮质发生,研究人员在体外从背侧或腹侧前脑器官体连续取样了20多个月的神经胶质和神经元谱系。在不同发育阶段的类器官体中观察到在人类原发性脑组织中发现的活跃染色质区域。研究人员使用此资源来绘制了疾病的遗传风险图谱并探究了进化保守性。此外,研究人员将染色质可及性与转录组学进行了整合,从而鉴定出可能的增强子-基因连锁以及调节人类皮质发生的转录因子。总体而言,该平台为以前难以达到的人类前脑发育阶段带来了基因调控动态的见解,以及神经精神疾病的特征。
 
附:英文原文

Title: Chromatin accessibility dynamics in a model of human forebrain development

Author: Alexandro E. Trevino, Nasa Sinnott-Armstrong, Jimena Andersen, Se-Jin Yoon, Nina Huber, Jonathan K. Pritchard, Howard Y. Chang, William J. Greenleaf, Sergiu P. Paca

Issue&Volume: 2020/01/24

Abstract: Forebrain development is characterized by highly synchronized cellular processes, which, if perturbed, can cause disease. To chart the regulatory activity underlying these events, we generated a map of accessible chromatin in human three-dimensional forebrain organoids. To capture corticogenesis, we sampled glial and neuronal lineages from dorsal or ventral forebrain organoids over 20 months in vitro. Active chromatin regions identified in human primary brain tissue were observed in organoids at different developmental stages. We used this resource to map genetic risk for disease and to explore evolutionary conservation. Moreover, we integrated chromatin accessibility with transcriptomics to identify putative enhancer-gene linkages and transcription factors that regulate human corticogenesis. Overall, this platform brings insights into gene-regulatory dynamics at previously inaccessible stages of human forebrain development, including signatures of neuropsychiatric disorders.

DOI: 10.1126/science.aay1645

Source: https://science.sciencemag.org/content/367/6476/eaay1645

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037