An environment-dependent transcriptional network specifies human microglia identity

被引：829

作者：

Gosselin, David ^{[1
]}

Skola, Dylan ^{[1
]}

Coufal, Nicole G. ^{[2
,3
]}

Holtman, Inge R. ^{[1
,4
]}

Schlachetzki, Johannes C. M. ^{[1
]}

Sajti, Eniko ^{[3
]}

Jaeger, Baptiste N. ^{[2
]}

O'Connor, Carolyn ^{[2
]}

Fitzpatrick, Conor ^{[2
]}

Pasillas, Martina P. ^{[1
]}

Pena, Monique ^{[2
]}

Adair, Amy ^{[2
]}

Gonda, David D. ^{[5
]}

Levy, Michael L. ^{[5
]}

Ransohoff, Richard M. ^{[6
]}

Gage, Fred H. ^{[2
]}

Glass, Christopher K. ^{[1
,7
]}

机构：

[1] Univ Calif San Diego, Dept Cellular & Mol Med, 9500 Gilman Dr, La Jolla, CA 92093 USA

[2] Salk Inst Biol Studies, Genet Lab, 10010 North Torrey Pines Rd, La Jolla, CA 92037 USA

[3] Univ Calif San Diego, Dept Pediat, 9500 Gilman Dr, La Jolla, CA 92093 USA

[4] Univ Groningen, Univ Med Ctr Groningen, Dept Neurosci, Sect Med Physiol, Groningen, Netherlands

[5] Univ Calif San Diego, Rady Childrens Hosp, Dept Neurosurg, San Diego, CA 92123 USA

[6] Biogen, Neuroimmunol, 225 Binney St, Cambridge, MA 02142 USA

[7] Univ Calif San Diego, Dept Med, 9500 Gilman Dr, La Jolla, CA 92093 USA

来源：

SCIENCE | 2017年 / 356卷 / 6344期

基金：

加拿大健康研究院;

关键词：

GENE-EXPRESSION; ALZHEIMERS-DISEASE; SUPER-ENHANCERS; CELL IDENTITY; MACROPHAGE; INFLAMMATION; ACTIVATION; SELECTION; LINEAGE; VIABILITY;

D O I：

10.1126/science.aal3222

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

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 microglia-specific 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.

引用

页码：1248 / 1259

页数：11

共 65 条

[51] Systems-Based Analyses of Brain Regions Functionally Impacted in Parkinson's Disease Reveals Underlying Causal Mechanisms [J].

Riley, Brigit E. ;

Gardai, Shyra J. ;

Emig-Agius, Dorothea ;

Bessarabova, Marina ;

Ivliev, Alexander E. ;

Schuele, Birgit ;

Alexander, Jeff ;

Wallace, William ;

Halliday, Glenda M. ;

Langston, J. William ;

Braxton, Scott ;

Yednock, Ted ;

Shaler, Thomas ;

Johnston, Jennifer A. .

PLOS ONE, 2014, 9 (08)

[52] Regulation of innate immune responses in the brain [J].

Rivest, Serge .

NATURE REVIEWS IMMUNOLOGY, 2009, 9 (06) :429-439

[53] Epigenomics Roadmap for regulation [J].

Romanoski, Casey E. ;

Glass, Christopher K. .

NATURE, 2015, 518 (7539) :314-316

[54] A Nurr1/CoREST Pathway in Microglia and Astrocytes Protects Dopaminergic Neurons from Inflammation-Induced Death [J].

Saijo, Kaoru ;

Winner, Beate ;

Carson, Christian T. ;

Collier, Jana G. ;

Boyer, Leah ;

Rosenfeld, Michael G. ;

Gage, Fred H. ;

Glass, Christopher K. .

CELL, 2009, 137 (01) :47-59

[55] RNA-Seq Data Mining: Downregulation of NeuroD6 Serves as a Possible Biomarker for Alzheimer's Disease Brains [J].

Satoh, Jun-ichi ;

Yamamoto, Yoji ;

Asahina, Naohiro ;

Kitano, Shouta ;

Kino, Yoshihiro .

DISEASE MARKERS, 2014, 2014

[56] Microglia Function in Central Nervous System Development and Plasticity [J].

Schafer, Dorothy P. ;

Stevens, Beth .

COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2015, 7 (10)

[57] Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner [J].

Schafer, Dorothy P. ;

Lehrman, Emily K. ;

Kautzman, Amanda G. ;

Koyama, Ryuta ;

Mardinly, Alan R. ;

Yamasaki, Ryo ;

Ransohoff, Richard M. ;

Greenberg, Michael E. ;

Barres, Ben A. ;

Stevens, Beth .

NEURON, 2012, 74 (04) :691-705

[58] A Lineage of Myeloid Cells Independent of Myb and Hematopoietic Stem Cells [J].

Schulz, Christian ;

Perdiguero, Elisa Gomez ;

Chorro, Laurent ;

Szabo-Rogers, Heather ;

Cagnard, Nicolas ;

Kierdorf, Katrin ;

Prinz, Marco ;

Wu, Bishan ;

Jacobsen, Sten Eirik W. ;

Pollard, Jeffrey W. ;

Frampton, Jon ;

Liu, Karen J. ;

Geissmann, Frederic .

SCIENCE, 2012, 336 (6077) :86-90

[59] Microglia Plasticity During Health one Disease: An Immunological Perspective [J].

Shemer, Anat ;

Erny, Daniel ;

Jung, Steffen ;

Prinz, Marco .

TRENDS IN IMMUNOLOGY, 2015, 36 (10) :614-624

[60] The transcription factor PU.1 is critical for viability and function of human brain microglia [J].

Smith, Amy M. ;

Gibbons, Hannah M. ;

Oldfield, Robyn L. ;

Bergin, Peter M. ;

Mee, Edward W. ;

Faull, Richard L. M. ;

Dragunow, Mike .

GLIA, 2013, 61 (06) :929-942

← 1 2 3 4 5 6 7 →