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Developmental Heterogeneity of Microglia and Brain Myeloid Cells Revealed by Deep Single-Cell RNA Sequencing.
Neuron ( IF 14.7 ) Pub Date : 2018-12-31 , DOI: 10.1016/j.neuron.2018.12.006 Qingyun Li 1 , Zuolin Cheng 2 , Lu Zhou 1 , Spyros Darmanis 3 , Norma F Neff 3 , Jennifer Okamoto 3 , Gunsagar Gulati 4 , Mariko L Bennett 1 , Lu O Sun 1 , Laura E Clarke 1 , Julia Marschallinger 5 , Guoqiang Yu 2 , Stephen R Quake 3 , Tony Wyss-Coray 5 , Ben A Barres 1
Neuron ( IF 14.7 ) Pub Date : 2018-12-31 , DOI: 10.1016/j.neuron.2018.12.006 Qingyun Li 1 , Zuolin Cheng 2 , Lu Zhou 1 , Spyros Darmanis 3 , Norma F Neff 3 , Jennifer Okamoto 3 , Gunsagar Gulati 4 , Mariko L Bennett 1 , Lu O Sun 1 , Laura E Clarke 1 , Julia Marschallinger 5 , Guoqiang Yu 2 , Stephen R Quake 3 , Tony Wyss-Coray 5 , Ben A Barres 1
Affiliation
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Microglia are increasingly recognized for their major contributions during brain development and neurodegenerative disease. It is currently unknown whether these functions are carried out by subsets of microglia during different stages of development and adulthood or within specific brain regions. Here, we performed deep single-cell RNA sequencing (scRNA-seq) of microglia and related myeloid cells sorted from various regions of embryonic, early postnatal, and adult mouse brains. We found that the majority of adult microglia expressing homeostatic genes are remarkably similar in transcriptomes, regardless of brain region. By contrast, early postnatal microglia are more heterogeneous. We discovered a proliferative-region-associated microglia (PAM) subset, mainly found in developing white matter, that shares a characteristic gene signature with degenerative disease-associated microglia (DAM). Such PAM have amoeboid morphology, are metabolically active, and phagocytose newly formed oligodendrocytes. This scRNA-seq atlas will be a valuable resource for dissecting innate immune functions in health and disease.
中文翻译：
小胶质细胞和脑髓样细胞的发育异质性由深层单细胞RNA测序揭示。
小胶质细胞因其在大脑发育和神经退行性疾病中的主要贡献而得到越来越多的认可。目前尚不清楚这些功能是在发育和成年的不同阶段还是在特定的大脑区域中由小胶质细胞的子集执行。在这里，我们对小胶质细胞和相关的骨髓细胞进行了深层单细胞RNA测序（scRNA-seq），这些细胞从胚胎，出生后早期和成年小鼠大脑的各个区域分选出来。我们发现，无论脑区如何，大多数表达稳态基因的成年小胶质细胞在转录组中都非常相似。相比之下，产后早期的小胶质细胞异质性更高。我们发现了一个与增生区域相关的小胶质细胞（PAM）子集，主要存在于发育中的白质中，与退化性疾病相关小胶质细胞（DAM）共享特征基因签名。这种PAM具有变形虫形态，具有代谢活性，并且吞噬新形成的少突胶质细胞。此scRNA-seq地图集将是解剖健康和疾病中固有免疫功能的宝贵资源。
更新日期：2019-01-01
中文翻译：
小胶质细胞和脑髓样细胞的发育异质性由深层单细胞RNA测序揭示。
小胶质细胞因其在大脑发育和神经退行性疾病中的主要贡献而得到越来越多的认可。目前尚不清楚这些功能是在发育和成年的不同阶段还是在特定的大脑区域中由小胶质细胞的子集执行。在这里，我们对小胶质细胞和相关的骨髓细胞进行了深层单细胞RNA测序（scRNA-seq），这些细胞从胚胎，出生后早期和成年小鼠大脑的各个区域分选出来。我们发现，无论脑区如何，大多数表达稳态基因的成年小胶质细胞在转录组中都非常相似。相比之下，产后早期的小胶质细胞异质性更高。我们发现了一个与增生区域相关的小胶质细胞（PAM）子集，主要存在于发育中的白质中，与退化性疾病相关小胶质细胞（DAM）共享特征基因签名。这种PAM具有变形虫形态，具有代谢活性，并且吞噬新形成的少突胶质细胞。此scRNA-seq地图集将是解剖健康和疾病中固有免疫功能的宝贵资源。
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