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。

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