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DOI10.1126/science.aal3222
An environment-dependent transcriptional network specifies human microglia identity
Gosselin D.; Skola D.; Coufal N.G.; Holtman I.R.; Schlachetzki J.C.M.; Sajti E.; Jaeger B.N.; O'Connor C.; Fitzpatrick C.; Pasillas M.P.; Pena M.; Adair A.; Gonda D.D.; Levy M.L.; Ransohoff R.M.; Gage F.H.; Glass C.K.
发表日期2017
ISSN0036-8075
起始页码1248
结束页码1259
卷号356期号:6344
英文摘要Microglia play essential roles in central nervous system (CNS) homeostasis and influence diverse aspects of neuronal function. However, the transcriptional mechanisms that specify human microglia phenotypes are largely unknown.We examined the transcriptomes and epigenetic landscapes of human microglia isolated from surgically resected brain tissue ex vivo and after transition to an in vitro environment. Transfer to a tissue culture environment resulted in rapid and extensive down-regulation of microgliaspecific genes that were induced in primitive mouse macrophages after migration into the fetal brain. Substantial subsets of these genes exhibited altered expression in neurodegenerative and behavioral diseases and were associated with noncoding risk variants. These findings reveal an environment-dependent transcriptional network specifying microglia-specific programs of gene expression and facilitate efforts to understand the roles of microglia in human brain diseases. © The Authors, some rights reserved.
英文关键词APOC1 protein; apolipoprotein E; chemokine receptor CX3CR1; CIITA protein; complementary DNA; early growth response factor 3; interferon regulatory factor 1; interferon regulatory factor 2; messenger RNA; myocyte enhancer factor 2; nuclear receptor related factor 1; osteonectin; P2RY12 protein; polyadenylated RNA; SALL1 protein; Sall3 protein; Smad1 protein; STAT3 protein; TMEM119 protein; transcription factor; transcription factor AP 1; transcription factor CTCF; transcription factor Maf; transcription factor MafB; transcription factor PU 1; transcription factor RelA; transcription factor RUNX2; transcriptome; transposase; unclassified drug; VSIG4 protein; brain; cells and cell components; gene expression; homeostasis; hominid; molecular analysis; nervous system; phenotype; rodent; allele; animal cell; animal tissue; Article; brain disease; brain tissue; chromatin immunoprecipitation; clinical article; comparative study; controlled study; degenerative disease; down regulation; enhancer region; environmental impact; epigenetics; gene expression; gene regulatory network; genetic transcription; human; human cell; human tissue; in vitro study; mental disease; microglia; mouse; neuropathology; nonhuman; primary culture; priority journal; RNA sequence; tissue culture; transcriptomics; animal; brain tumor; C57BL mouse; cell culture; cytology; environment; epilepsy; female; gene expression profiling; gene expression regulation; gene regulatory network; genetics; male; microglia; pathophysiology; physiology; Animals; Brain Neoplasms; Cells, Cultured; Environment; Epilepsy; Female; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; Humans; Male; Mice; Mice, Inbred C57BL; Microglia
语种英语
来源期刊Science
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/243839
作者单位Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093-0651, United States; Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, San Diego, CA 92037-1002, United States; Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093-0651, United States; Department of Neuroscience, Section Medical Physiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands; Department of Neurosurgery, University of California, San Diego-Rady Children's Hospital, San Diego, CA 92123, United States; Neuroimmunology, Biogen, 225 Binney Street, Cambridge, MA 02142, United States; Department of Medicine, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093-0651, United States
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Gosselin D.,Skola D.,Coufal N.G.,et al. An environment-dependent transcriptional network specifies human microglia identity[J],2017,356(6344).
APA Gosselin D..,Skola D..,Coufal N.G..,Holtman I.R..,Schlachetzki J.C.M..,...&Glass C.K..(2017).An environment-dependent transcriptional network specifies human microglia identity.Science,356(6344).
MLA Gosselin D.,et al."An environment-dependent transcriptional network specifies human microglia identity".Science 356.6344(2017).
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