Developmental heterogeneity of microglia and brain myeloid cells revealed by deep single-cell RNA sequencing
| Autor: | Qingyun Li, Mariko L. Bennett, Lu Zhou, Lu O. Sun, Gunsagar S. Gulati, Stephen R. Quake, Spyros Darmanis, Guoqiang Yu, Ben A. Barres, Norma F. Neff, Tony Wyss-Coray, Julia Marschallinger, Laura E. Clarke, Jennifer Okamoto, Zuolin Cheng |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Myeloid Cell Mice Transgenic Biology Transcriptome 03 medical and health sciences Mice 0302 clinical medicine Phagocytosis Antigens CD medicine Animals Cluster Analysis Computer Simulation Gene Regulatory Networks Myeloid Cells Gene Cell Proliferation Innate immune system Microglia Sequence Analysis RNA General Neuroscience RNA Brain Gene Expression Regulation Developmental High-Throughput Nucleotide Sequencing Gene signature Cell cycle Embryo Mammalian Embryonic stem cell Cell biology Mice Inbred C57BL Oligodendroglia 030104 developmental biology medicine.anatomical_structure Animals Newborn nervous system Choroid Plexus Neuroscience 030217 neurology & neurosurgery Algorithms |
| DOI: | 10.1101/406363 |
| Popis: | SummaryMicroglia are increasingly recognized for their major contributions during brain development and neurodegenerative disease. It is currently unknown if 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, postnatal, and adult mouse brains. We found that the majority of adult microglia with homeostatic signatures are remarkably similar in transcriptomes, regardless of brain region. By contrast, postnatal microglia represent a more heterogeneous population. We discovered that postnatal white matter-associated microglia (WAM) are strikingly different from microglia in other regions and express genes enriched in degenerative disease-associated microglia. These postnatal WAM have distinct 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.HighlightsMyeloid scRNA-seq atlas across brain regions and developmental stagesLimited transcriptomic heterogeneity of homeostatic microglia in the adult brainPhase-specific gene sets of proliferating microglia along cell cycle pseudotimePhagocytic postnatal white matter-associated microglia sharing DAM gene signatures |
| Databáze: | OpenAIRE |
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