小柯机器人

皮质类器官体细胞应激损害分子亚型分化
2020-02-10 09:48

美国加州大学旧金山分校Arnold R. Kriegstein团队的一项最新工作揭示,皮质类器官体细胞应激能够损害分子亚型分化。 相关论文于2020年1月29日在线发表于国际学术期刊《自然》。

研究人员分析了来自不同发育时期和皮层区域的单个原代人类皮层细胞的转录组。研究人员发现皮质发育的特征是祖细胞成熟的轨迹、各种细胞亚型的出现和新生神经元的区域特化。相比之下,类器官体包含广泛的细胞类别,但没有概括不同的细胞亚型身份和适当的祖细胞成熟。尽管皮层区域的分子标记出现在类器官体神经元中,但它们在空间上并未分离。类器官体也异位激活细胞应激途径,从而损害细胞类型分化。但是,类器官体压力和亚型缺陷可通过移植到小鼠皮质中得到缓解。这些数据集和分析工具一起提供了一个框架,从而用于评估和提高作为人类大脑发育模型的皮质类器官体的准确性。

据介绍,皮质类器官体是自组织的三维培养物,其模拟正在发育的人类大脑皮层的特征。然而,类器官体模型的保真度仍不清楚。

附:英文原文

Title: Cell stress in cortical organoids impairs molecular subtype specification

Author: Aparna Bhaduri, Madeline G. Andrews, Walter Mancia Leon, Diane Jung, David Shin, Denise Allen, Dana Jung, Galina Schmunk, Maximilian Haeussler, Jahan Salma, Alex A. Pollen, Tomasz J. Nowakowski, Arnold R. Kriegstein

Issue&Volume: 2020-01-29

Abstract: Cortical organoids are self-organizing three-dimensional cultures that model features of the developing human cerebral cortex1,2. However, the fidelity of organoid models remains unclear3,4,5. Here we analyse the transcriptomes of individual primary human cortical cells from different developmental periods and cortical areas. We find that cortical development is characterized by progenitor maturation trajectories, the emergence of diverse cell subtypes and areal specification of newborn neurons. By contrast, organoids contain broad cell classes, but do not recapitulate distinct cellular subtype identities and appropriate progenitor maturation. Although the molecular signatures of cortical areas emerge in organoid neurons, they are not spatially segregated. Organoids also ectopically activate cellular stress pathways, which impairs cell-type specification. However, organoid stress and subtype defects are alleviated by transplantation into the mouse cortex. Together, these datasets and analytical tools provide a framework for evaluating and improving the accuracy of cortical organoids as models of human brain development.

DOI: 10.1038/s41586-020-1962-0

Source: https://www.nature.com/articles/s41586-020-1962-0

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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