@article{b56c4519b6fa4eecb611666a956e7693,
title = "Developmental Heterogeneity of Microglia and Brain Myeloid Cells Revealed by Deep Single-Cell RNA Sequencing",
abstract = "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.",
keywords = "brain myeloid cells, brain regions, cell cycle, development, disease-associated microglia, heterogeneity, microglia, phagocytosis, proliferative-region-associated microglia, single-cell RNA-seq",
author = "Qingyun Li and Zuolin Cheng and Lu Zhou and Spyros Darmanis and Neff, {Norma F.} and Jennifer Okamoto and Gunsagar Gulati and Bennett, {Mariko L.} and Sun, {Lu O.} and Clarke, {Laura E.} and Julia Marschallinger and Guoqiang Yu and Quake, {Stephen R.} and Tony Wyss-Coray and Barres, {Ben A.}",
note = "Funding Information: We thank Ryosuke Kita for making the Myeloid Single-cell RNA-seq webpage; Steven Sloan, Christopher Bohlen, Frederick Christian Bennett, and Mengmeng Fu for their help and insightful feedback on the manuscript; and David Simon, Tal Iram, John Pluvinage, Jianjin Shi, Wan-Jin Lu, and Charles Kwok Fai Chan for discussions and generous help. We thank the Stanford Shared FACS Facility, particularly Brandon Carter and Meredith Weglarz, for their excellent service; John Mulholland and Kitty Lee from the Stanford Cell Sciences Imaging Facility for help with confocal imaging; and Chi-Li Chiu from BITPLANE for help with Imaris software. This work is funded by the JPB Foundation (B.A.B.), Adelson Medical Research Foundation (B.A.B.), Vincent J. Coates Foundation (B.A.B.), NIH ( R01 DA015043 ; B.A.B.), the Veterans Administration (T.W.-C.), the NOMIS Foundation (T.W.-C.), NIH ( R01 MH110504 ; G.Y.), the Helen Hay Whitney Foundation (L.O.S.), National Multiple Sclerosis Society (L.O.S.), and the Life Science Research Foundation (L.E.C.). Q.L. is supported by a Stanford Medicine Dean{\textquoteright}s Fellowship . Funding Information: We thank Ryosuke Kita for making the Myeloid Single-cell RNA-seq webpage; Steven Sloan, Christopher Bohlen, Frederick Christian Bennett, and Mengmeng Fu for their help and insightful feedback on the manuscript; and David Simon, Tal Iram, John Pluvinage, Jianjin Shi, Wan-Jin Lu, and Charles Kwok Fai Chan for discussions and generous help. We thank the Stanford Shared FACS Facility, particularly Brandon Carter and Meredith Weglarz, for their excellent service; John Mulholland and Kitty Lee from the Stanford Cell Sciences Imaging Facility for help with confocal imaging; and Chi-Li Chiu from BITPLANE for help with Imaris software. This work is funded by the JPB Foundation (B.A.B.), Adelson Medical Research Foundation (B.A.B.), Vincent J. Coates Foundation (B.A.B.), NIH (R01 DA015043; B.A.B.), the Veterans Administration (T.W.-C.), the NOMIS Foundation (T.W.-C.), NIH (R01 MH110504; G.Y.), the Helen Hay Whitney Foundation (L.O.S.), National Multiple Sclerosis Society (L.O.S.), and the Life Science Research Foundation (L.E.C.). Q.L. is supported by a Stanford Medicine Dean's Fellowship. Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2019",
month = jan,
day = "16",
doi = "10.1016/j.neuron.2018.12.006",
language = "English",
volume = "101",
pages = "207--223.e10",
journal = "Neuron",
issn = "0896-6273",
number = "2",
}