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衰老和神经变性中疾病相关小胶质细胞和疾病炎性巨噬细胞的双重个体发育
作者:小柯机器人 发布时间:2022/8/7 18:22:20

新加坡科技与研究中心Florent Ginhoux团队近日取得重要工作进展,他们报道了衰老和神经变性中疾病相关小胶质细胞和疾病炎性巨噬细胞的双重个体发育。相关论文2022年8月4日在线发表于《免疫》杂志上。

研究人员生成了一个小鼠脑髓系scRNA-seq整合数据集来系统地描绘脑巨噬细胞群。他们表明,在小鼠阿尔茨海默病模型中检测到的先前确定的疾病相关小胶质细胞(DAM)群体实际上包含两个个体遗传学和功能上不同的细胞谱系:在骨髓细胞上表达的胚胎来源触发受体 2(TREM2)依赖的DAM表达神经保护特征,和单核细胞来源的表达TREM2的疾病炎性巨噬细胞(DIM)在衰老过程中在大脑中积累。这两个不同的种群似乎在人脑中也很保守。

在此工作中,研究人员生成了脑髓细胞在发育、内稳态和疾病中异质性的个体发育解析模型,并确定了用于治疗神经退行性疾病的细胞靶点。

据介绍,脑巨噬细胞群包括实质小胶质细胞、边界相关巨噬细胞和募集的单核细胞来源细胞。它们共同控制着大脑的发育和内稳态,但也与衰老发病机制和神经退行性病变有关。每个群体在不同环境下的表型、定位和功能尚不清楚。

附:英文原文

Title: Dual ontogeny of disease-associated microglia and disease inflammatory macrophages in aging and neurodegeneration

Author: Aymeric Silvin, Stefan Uderhardt, Cecile Piot, Sandro Da Mesquita, Katharine Yang, Laufey Geirsdottir, Kevin Mulder, David Eyal, Zhaoyuan Liu, Cecile Bridlance, Morgane Sonia Thion, Xiao Meng Zhang, Wan Ting Kong, Marc Deloger, Vasco Fontes, Assaf Weiner, Rachel Ee, Regine Dress, Jing Wen Hang, Akhila Balachander, Svetoslav Chakarov, Benoit Malleret, Garett Dunsmore, Olivier Cexus, Jinmiao Chen, Sonia Garel, Charles Antoine Dutertre, Ido Amit, Jonathan Kipnis, Florent Ginhoux

Issue&Volume: 2022-08-04

Abstract: Brain macrophage populations include parenchymal microglia, border-associated macrophages,and recruited monocyte-derived cells; together, they control brain development andhomeostasis but are also implicated in aging pathogenesis and neurodegeneration. Thephenotypes, localization, and functions of each population in different contexts haveyet to be resolved. We generated a murine brain myeloid scRNA-seq integration to systematicallydelineate brain macrophage populations. We show that the previously identified disease-associatedmicroglia (DAM) population detected in murine Alzheimer’s disease models actuallycomprises two ontogenetically and functionally distinct cell lineages: embryonicallyderived triggering receptor expressed on myeloid cells 2 (TREM2)-dependent DAM expressinga neuroprotective signature and monocyte-derived TREM2-expressing disease inflammatorymacrophages (DIMs) accumulating in the brain during aging. These two distinct populationsappear to also be conserved in the human brain. Herein, we generate an ontogeny-resolvedmodel of brain myeloid cell heterogeneity in development, homeostasis, and diseaseand identify cellular targets for the treatment of neurodegeneration.

DOI: 10.1016/j.immuni.2022.07.004

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00337-5

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新IF:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx