荷兰儿科肿瘤中心Benedetta Artegiani、Hans Clevers、Delilah Hendriks团队在研究中取得进展。他们利用体细胞生产了具有扩张性的胎儿大脑类器官。相关论文发表在2024年1月8日出版的《细胞》杂志上。
研究人员建立了健康胎儿大脑类器官的体外自我组装（FeBOs）系统，表征了体内细胞异质性和复杂组织的各个方面。FeBO可以长期扩展。FeBO的生长需要保持组织完整性，从而确保产生类似组织的细胞外基质（ECM）龛，最终实现FeBO的扩展。
从中枢神经系统（CNS）的不同区域（包括背侧和腹侧前脑）提取的FeBO能保持其区域特性，并能探究位置特性的各种特征。利用CRISPR-Cas9，研究人员建立了用于脑癌研究的合成突变型FeBO株系。总之，FeBO是一个互补的中枢神经系统类器官平台。
研究人员表示，人类大脑的发育需要神经祖细胞的协调、大规模扩增并同时建立多细胞组织结构。多种体细胞组织可直接产生具有持续扩张性的器官组织，而目前脑类器官组织只能由多能干细胞产生。
附：英文原文
Title: Human fetal brain self-organizes into long-term expanding organoids
Author: Delilah Hendriks, Anna Pagliaro, Francesco Andreatta, Ziliang Ma, Joey van Giessen, Simone Massalini, Carmen López-Iglesias, Gijs J.F. van Son, Jeff DeMartino, J. Mirjam A. Damen, Iris Zoutendijk, Nadzeya Staliarova, Annelien L. Bredenoord, Frank C.P. Holstege, Peter J. Peters, Thanasis Margaritis, Susana Chuva de Sousa Lopes, Wei Wu, Hans Clevers, Benedetta Artegiani
Issue&Volume: 2024-01-08
Abstract: Human brain development involves an orchestrated, massive neural progenitor expansion while a multi-cellular tissue architecture is established. Continuously expanding organoids can be grown directly from multiple somatic tissues, yet to date, brain organoids can solely be established from pluripotent stem cells. Here, we show that healthy human fetal brain in vitro self-organizes into organoids (FeBOs), phenocopying aspects of in vivo cellular heterogeneity and complex organization. FeBOs can be expanded over long time periods. FeBO growth requires maintenance of tissue integrity, which ensures production of a tissue-like extracellular matrix (ECM) niche, ultimately endowing FeBO expansion. FeBO lines derived from different areas of the central nervous system (CNS), including dorsal and ventral forebrain, preserve their regional identity and allow to probe aspects of positional identity. Using CRISPR-Cas9, we showcase the generation of syngeneic mutant FeBO lines for the study of brain cancer. Taken together, FeBOs constitute a complementary CNS organoid platform.
DOI: 10.1016/j.cell.2023.12.012
Source: https://www.cell.com/cell/fulltext/S0092-8674(23)01344-2
来源：科学网 小柯机器人