美国加州大学旧金山分校Tomasz J. Nowakowski团队发现，人类小胶质细胞状态在不同的实验模型中是保守的，并在嵌合类器官中调节神经干细胞的反应。2021年9月17日，国际知名学术期刊《细胞—干细胞》在线发表了这一成果。

研究人员比较了人类小胶质细胞在不同培养模型中的状态，包括培养的原代和多能干细胞衍生的小胶质细胞。研究人员开发了这些不同模型的基因表达特征的"报告卡"，用于促进它们在不同实验模型、扰动和疾病条件下的反应特征。将人类小胶质细胞异种移植到大脑类器官中，这使研究人员能够在体外描述发育中小胶质细胞的关键转录程序，并发现小胶质细胞诱导神经干细胞的转录变化，减少干扰素信号反应基因。小胶质细胞还通过调节突触密度加速了大脑类器官中同步振荡网络活动的出现。

据悉，小胶质细胞是大脑中的常驻巨噬细胞，在早期发育中出现并通过改变其分子和表型状态对局部环境做出反应。关于小胶质细胞在发育过程中的多样性和功能的基本问题仍然没有答案，因为目前缺乏实验策略来审视它们与其他细胞类型的相互作用以及对体外干扰的反应。

附：英文原文

Title: Human microglia states are conserved across experimental models and regulate neural stem cell responses in chimeric organoids

Author: Galina Popova, Sarah S. Soliman, Chang N. Kim, Matthew G. Keefe, Kelsey M. Hennick, Samhita Jain, Tao Li, Dario Tejera, David Shin, Bryant B. Chhun, Christopher S. McGinnis, Matthew Speir, Zev J. Gartner, Shalin B. Mehta, Maximilian Haeussler, Keith B. Hengen, Richard R. Ransohoff, Xianhua Piao, Tomasz J. Nowakowski

Issue&Volume: 2021-09-17

Abstract: Microglia are resident macrophages in the brain that emerge in early development andrespond to the local environment by altering their molecular and phenotypic states.Fundamental questions about microglia diversity and function during development remainunanswered because we lack experimental strategies to interrogate their interactionswith other cell types and responses to perturbations ex vivo. We compared human microglia states across culture models, including cultured primaryand pluripotent stem cell-derived microglia. We developed a “report card” of geneexpression signatures across these distinct models to facilitate characterizationof their responses across experimental models, perturbations, and disease conditions.Xenotransplantation of human microglia into cerebral organoids allowed us to characterizekey transcriptional programs of developing microglia in vitro and reveal that microglia induce transcriptional changes in neural stem cells anddecrease interferon signaling response genes. Microglia additionally accelerate theemergence of synchronized oscillatory network activity in brain organoids by modulatingsynaptic density.

DOI: 10.1016/j.stem.2021.08.015

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00376-3