德国弗莱堡大学Marco Prinz、Daniel Erny、以色列威兹曼科学研究所Ido Amit等研究人员利用跨物种单细胞分析，揭示了灵长类小胶质细胞程序的分化。 该研究于2019年12月12日发表于国际一流学术期刊《细胞》上。
研究人员描述了跨越4.5亿多年进化的10个物种的小胶质细胞形态学和转录程序。研究人员发现小胶质细胞表达从啮齿动物到人类的直系同源基因的保守核心基因程序，包括与神经胶质和神经元之间的相互作用相关的配体和受体。在大多数物种中，小胶质细胞显示单个显性转录状态，而人小胶质细胞表现出明显的异质性。此外，研究人员观察到与灵长类小胶质细胞相比，啮齿动物的几个基因模块存在显著差异，包括补体、吞噬和对神经变性的易感基因，例如阿尔茨海默氏病和帕金森氏病。这项研究为整个进化过程中小胶质细胞的保守和分化途径提供了重要的资源，对基于小胶质细胞疗法在人类中的未来发展具有重要意义。
据介绍，小胶质细胞是驻留在大脑中的免疫细胞，在许多生理和病理性大脑过程（包括神经变性）中都至关重要。
附：英文原文
Title: Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program
Author: Laufey Geirsdottir, Eyal David, Hadas Keren-Shaul, Assaf Weiner, Stefan Cornelius Bohlen, Jana Neuber, Adam Balic, Amir Giladi, Fadi Sheban, Charles-Antoine Dutertre, Christine Pfeifle, Francesca Peri, Antonella Raffo-Romero, Jacopo Vizioli, Kaspar Matiasek, Christian Scheiwe, Stephan Meckel, Kerstin Mtz-Rensing, Franziska van der Meer, Finnbogi Rutur Thormodsson, Christine Stadelmann, Noga Zilkha, Tali Kimchi, Florent Ginhoux, Igor Ulitsky, Daniel Erny, Ido Amit, Marco Prinz
Issue&Volume: 2019/12/12
Abstract: Microglia, the brain-resident immune cells, are critically involved in many physiologicaland pathological brain processes, including neurodegeneration. Here we characterizemicroglia morphology and transcriptional programs across ten species spanning morethan 450 million years of evolution. We find that microglia express a conserved coregene program of orthologous genes from rodents to humans, including ligands and receptorsassociated with interactions between glia and neurons. In most species, microgliashow a single dominant transcriptional state, whereas human microglia display significantheterogeneity. In addition, we observed notable differences in several gene modulesof rodents compared with primate microglia, including complement, phagocytic, andsusceptibility genes to neurodegeneration, such as Alzheimer’s and Parkinson’s disease.Our study provides an essential resource of conserved and divergent microglia pathwaysacross evolution, with important implications for future development of microglia-basedtherapies in humans.
DOI: 10.1016/j.cell.2019.11.010
Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31231-0