Transcriptomic analysis of purified human cortical microglia reveals age-associated changes
Microglia are the macrophages of the CNS, with innate neuroimmune function, and play important roles in tissue homeostasis, CNS development and neurodegeneration. Here human microglial gene expression profiles were generated. Human and mouse microglia were highly similar, except for aging-regulated...
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| Veröffentlicht in: | Nature neuroscience 2017-08, Vol.20 (8), p.1162-1171 |
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| creator | Galatro, Thais F Holtman, Inge R Lerario, Antonio M Vainchtein, Ilia D Brouwer, Nieske Sola, Paula R Veras, Mariana M Pereira, Tulio F Leite, Renata E P Möller, Thomas Wes, Paul D Sogayar, Mari C Laman, Jon D den Dunnen, Wilfred Pasqualucci, Carlos A Oba-Shinjo, Sueli M Boddeke, Erik W G M Marie, Suely K N Eggen, Bart J L |
| description | Microglia are the macrophages of the CNS, with innate neuroimmune function, and play important roles in tissue homeostasis, CNS development and neurodegeneration. Here human microglial gene expression profiles were generated. Human and mouse microglia were highly similar, except for aging-regulated genes, indicating that microglial aging differs between humans and mice.
Microglia are essential for CNS homeostasis and innate neuroimmune function, and play important roles in neurodegeneration and brain aging. Here we present gene expression profiles of purified microglia isolated at autopsy from the parietal cortex of 39 human subjects with intact cognition. Overall, genes expressed by human microglia were similar to those in mouse, including established microglial genes
CX3CR1
,
P2RY12
and
ITGAM
(
CD11B
). However, a number of immune genes, not identified as part of the mouse microglial signature, were abundantly expressed in human microglia, including
TLR
,
Fcγ
and
SIGLEC
receptors, as well as
TAL1
and
IFI16
, regulators of proliferation and cell cycle. Age-associated changes in human microglia were enriched for genes involved in cell adhesion, axonal guidance, cell surface receptor expression and actin (dis)assembly. Limited overlap was observed in microglial genes regulated during aging between mice and humans, indicating that human and mouse microglia age differently. |
| doi_str_mv | 10.1038/nn.4597 |
| format | Article |
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Microglia are essential for CNS homeostasis and innate neuroimmune function, and play important roles in neurodegeneration and brain aging. Here we present gene expression profiles of purified microglia isolated at autopsy from the parietal cortex of 39 human subjects with intact cognition. Overall, genes expressed by human microglia were similar to those in mouse, including established microglial genes
CX3CR1
,
P2RY12
and
ITGAM
(
CD11B
). However, a number of immune genes, not identified as part of the mouse microglial signature, were abundantly expressed in human microglia, including
TLR
,
Fcγ
and
SIGLEC
receptors, as well as
TAL1
and
IFI16
, regulators of proliferation and cell cycle. Age-associated changes in human microglia were enriched for genes involved in cell adhesion, axonal guidance, cell surface receptor expression and actin (dis)assembly. Limited overlap was observed in microglial genes regulated during aging between mice and humans, indicating that human and mouse microglia age differently.</description><identifier>ISSN: 1097-6256</identifier><identifier>EISSN: 1546-1726</identifier><identifier>DOI: 10.1038/nn.4597</identifier><identifier>PMID: 28671693</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>38/39 ; 38/91 ; 631/1647/2217/2018 ; 631/337/2019 ; 631/378/2596/1953 ; 631/378/371 ; Actin ; Age ; Aging ; Aging - physiology ; Analysis ; Animal Genetics and Genomics ; Autopsies ; Autopsy ; Axon guidance ; Axons - metabolism ; Behavioral Sciences ; Biological Techniques ; Biomedicine ; Brain ; Brain - metabolism ; CD11b antigen ; CD11b Antigen - genetics ; Cell adhesion ; Cell adhesion & migration ; Cell cycle ; Cell Cycle - genetics ; Cell surface ; Central nervous system ; Cognition ; Cortex (parietal) ; CX3CR1 protein ; Gene expression ; Gene Expression - genetics ; Gene Expression Profiling ; Genes ; Homeostasis ; Humans ; Microglia ; Microglia - metabolism ; Neurobiology ; Neurodegeneration ; Neurosciences ; Receptors ; Regulators ; resource</subject><ispartof>Nature neuroscience, 2017-08, Vol.20 (8), p.1162-1171</ispartof><rights>Springer Nature America, Inc. 2017</rights><rights>COPYRIGHT 2017 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Aug 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c509t-40b4b37243e5c3287cc2dd5f757573eafc93148c07915057bcc0f0ab63791cdb3</citedby><cites>FETCH-LOGICAL-c509t-40b4b37243e5c3287cc2dd5f757573eafc93148c07915057bcc0f0ab63791cdb3</cites><orcidid>0000-0002-8363-4329</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nn.4597$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nn.4597$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28671693$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Galatro, Thais F</creatorcontrib><creatorcontrib>Holtman, Inge R</creatorcontrib><creatorcontrib>Lerario, Antonio M</creatorcontrib><creatorcontrib>Vainchtein, Ilia D</creatorcontrib><creatorcontrib>Brouwer, Nieske</creatorcontrib><creatorcontrib>Sola, Paula R</creatorcontrib><creatorcontrib>Veras, Mariana M</creatorcontrib><creatorcontrib>Pereira, Tulio F</creatorcontrib><creatorcontrib>Leite, Renata E P</creatorcontrib><creatorcontrib>Möller, Thomas</creatorcontrib><creatorcontrib>Wes, Paul D</creatorcontrib><creatorcontrib>Sogayar, Mari C</creatorcontrib><creatorcontrib>Laman, Jon D</creatorcontrib><creatorcontrib>den Dunnen, Wilfred</creatorcontrib><creatorcontrib>Pasqualucci, Carlos A</creatorcontrib><creatorcontrib>Oba-Shinjo, Sueli M</creatorcontrib><creatorcontrib>Boddeke, Erik W G M</creatorcontrib><creatorcontrib>Marie, Suely K N</creatorcontrib><creatorcontrib>Eggen, Bart J L</creatorcontrib><title>Transcriptomic analysis of purified human cortical microglia reveals age-associated changes</title><title>Nature neuroscience</title><addtitle>Nat Neurosci</addtitle><addtitle>Nat Neurosci</addtitle><description>Microglia are the macrophages of the CNS, with innate neuroimmune function, and play important roles in tissue homeostasis, CNS development and neurodegeneration. Here human microglial gene expression profiles were generated. Human and mouse microglia were highly similar, except for aging-regulated genes, indicating that microglial aging differs between humans and mice.
Microglia are essential for CNS homeostasis and innate neuroimmune function, and play important roles in neurodegeneration and brain aging. Here we present gene expression profiles of purified microglia isolated at autopsy from the parietal cortex of 39 human subjects with intact cognition. Overall, genes expressed by human microglia were similar to those in mouse, including established microglial genes
CX3CR1
,
P2RY12
and
ITGAM
(
CD11B
). However, a number of immune genes, not identified as part of the mouse microglial signature, were abundantly expressed in human microglia, including
TLR
,
Fcγ
and
SIGLEC
receptors, as well as
TAL1
and
IFI16
, regulators of proliferation and cell cycle. Age-associated changes in human microglia were enriched for genes involved in cell adhesion, axonal guidance, cell surface receptor expression and actin (dis)assembly. Limited overlap was observed in microglial genes regulated during aging between mice and humans, indicating that human and mouse microglia age differently.</description><subject>38/39</subject><subject>38/91</subject><subject>631/1647/2217/2018</subject><subject>631/337/2019</subject><subject>631/378/2596/1953</subject><subject>631/378/371</subject><subject>Actin</subject><subject>Age</subject><subject>Aging</subject><subject>Aging - physiology</subject><subject>Analysis</subject><subject>Animal Genetics and Genomics</subject><subject>Autopsies</subject><subject>Autopsy</subject><subject>Axon guidance</subject><subject>Axons - metabolism</subject><subject>Behavioral Sciences</subject><subject>Biological Techniques</subject><subject>Biomedicine</subject><subject>Brain</subject><subject>Brain - metabolism</subject><subject>CD11b antigen</subject><subject>CD11b Antigen - genetics</subject><subject>Cell adhesion</subject><subject>Cell adhesion & migration</subject><subject>Cell cycle</subject><subject>Cell Cycle - genetics</subject><subject>Cell surface</subject><subject>Central nervous system</subject><subject>Cognition</subject><subject>Cortex (parietal)</subject><subject>CX3CR1 protein</subject><subject>Gene expression</subject><subject>Gene Expression - genetics</subject><subject>Gene Expression Profiling</subject><subject>Genes</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Microglia</subject><subject>Microglia - metabolism</subject><subject>Neurobiology</subject><subject>Neurodegeneration</subject><subject>Neurosciences</subject><subject>Receptors</subject><subject>Regulators</subject><subject>resource</subject><issn>1097-6256</issn><issn>1546-1726</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNptkV9rFTEQxYMotlbxG8iCD9aHveZ_No-lWC0UBK1PPoTZbLJN2U2uyW6x395cWq23yDwkzPzOgZmD0GuCNwSz7kOMGy60eoIOieCyJYrKp_WPtWolFfIAvSjlGmOsRKefowPaSUWkZofox2WGWGwO2yXNwTYQYbotoTTJN9s1Bx_c0FytM8TGprwEC1NTuZzGKUCT3Y2DqTQwuhZKSTbAUnl7BXF05SV65uvUvbp_j9D3s4-Xp5_biy-fzk9PLlorsF5ajnveM0U5c8Iy2ilr6TAIr0Qt5sBbzQjvLFaaCCxUby32GHrJasMOPTtCx3e-25x-rq4sZg7FummC6NJaDKk6ITRmtKJvH6HXac115x3FpcBSUfxAjTA5E6JPSwa7MzUnXGuqMZa8Upv_ULUGVy-UovOh9vcE7_cElVncr2WEtRRz_u3rPvvujq2nLiU7b7Y5zJBvDcFmF7mJ0ewir-Sb-5XWfnbDX-5Pxg_nKXVUc8n_7PzI6zeySrF9</recordid><startdate>20170801</startdate><enddate>20170801</enddate><creator>Galatro, 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analysis of purified human cortical microglia reveals age-associated changes</title><author>Galatro, Thais F ; Holtman, Inge R ; Lerario, Antonio M ; Vainchtein, Ilia D ; Brouwer, Nieske ; Sola, Paula R ; Veras, Mariana M ; Pereira, Tulio F ; Leite, Renata E P ; Möller, Thomas ; Wes, Paul D ; Sogayar, Mari C ; Laman, Jon D ; den Dunnen, Wilfred ; Pasqualucci, Carlos A ; Oba-Shinjo, Sueli M ; Boddeke, Erik W G M ; Marie, Suely K N ; Eggen, Bart J L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c509t-40b4b37243e5c3287cc2dd5f757573eafc93148c07915057bcc0f0ab63791cdb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>38/39</topic><topic>38/91</topic><topic>631/1647/2217/2018</topic><topic>631/337/2019</topic><topic>631/378/2596/1953</topic><topic>631/378/371</topic><topic>Actin</topic><topic>Age</topic><topic>Aging</topic><topic>Aging - physiology</topic><topic>Analysis</topic><topic>Animal Genetics and Genomics</topic><topic>Autopsies</topic><topic>Autopsy</topic><topic>Axon guidance</topic><topic>Axons - metabolism</topic><topic>Behavioral Sciences</topic><topic>Biological Techniques</topic><topic>Biomedicine</topic><topic>Brain</topic><topic>Brain - metabolism</topic><topic>CD11b antigen</topic><topic>CD11b Antigen - genetics</topic><topic>Cell adhesion</topic><topic>Cell adhesion & migration</topic><topic>Cell cycle</topic><topic>Cell Cycle - genetics</topic><topic>Cell surface</topic><topic>Central nervous system</topic><topic>Cognition</topic><topic>Cortex (parietal)</topic><topic>CX3CR1 protein</topic><topic>Gene expression</topic><topic>Gene Expression - genetics</topic><topic>Gene Expression Profiling</topic><topic>Genes</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Microglia</topic><topic>Microglia - 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cortical microglia reveals age-associated changes</atitle><jtitle>Nature neuroscience</jtitle><stitle>Nat Neurosci</stitle><addtitle>Nat Neurosci</addtitle><date>2017-08-01</date><risdate>2017</risdate><volume>20</volume><issue>8</issue><spage>1162</spage><epage>1171</epage><pages>1162-1171</pages><issn>1097-6256</issn><eissn>1546-1726</eissn><abstract>Microglia are the macrophages of the CNS, with innate neuroimmune function, and play important roles in tissue homeostasis, CNS development and neurodegeneration. Here human microglial gene expression profiles were generated. Human and mouse microglia were highly similar, except for aging-regulated genes, indicating that microglial aging differs between humans and mice.
Microglia are essential for CNS homeostasis and innate neuroimmune function, and play important roles in neurodegeneration and brain aging. Here we present gene expression profiles of purified microglia isolated at autopsy from the parietal cortex of 39 human subjects with intact cognition. Overall, genes expressed by human microglia were similar to those in mouse, including established microglial genes
CX3CR1
,
P2RY12
and
ITGAM
(
CD11B
). However, a number of immune genes, not identified as part of the mouse microglial signature, were abundantly expressed in human microglia, including
TLR
,
Fcγ
and
SIGLEC
receptors, as well as
TAL1
and
IFI16
, regulators of proliferation and cell cycle. Age-associated changes in human microglia were enriched for genes involved in cell adhesion, axonal guidance, cell surface receptor expression and actin (dis)assembly. Limited overlap was observed in microglial genes regulated during aging between mice and humans, indicating that human and mouse microglia age differently.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>28671693</pmid><doi>10.1038/nn.4597</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-8363-4329</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1097-6256 |
| ispartof | Nature neuroscience, 2017-08, Vol.20 (8), p.1162-1171 |
| issn | 1097-6256 1546-1726 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1915559032 |
| source | MEDLINE; Nature Journals Online; SpringerLink Journals - AutoHoldings |
| subjects | 38/39 38/91 631/1647/2217/2018 631/337/2019 631/378/2596/1953 631/378/371 Actin Age Aging Aging - physiology Analysis Animal Genetics and Genomics Autopsies Autopsy Axon guidance Axons - metabolism Behavioral Sciences Biological Techniques Biomedicine Brain Brain - metabolism CD11b antigen CD11b Antigen - genetics Cell adhesion Cell adhesion & migration Cell cycle Cell Cycle - genetics Cell surface Central nervous system Cognition Cortex (parietal) CX3CR1 protein Gene expression Gene Expression - genetics Gene Expression Profiling Genes Homeostasis Humans Microglia Microglia - metabolism Neurobiology Neurodegeneration Neurosciences Receptors Regulators resource |
| title | Transcriptomic analysis of purified human cortical microglia reveals age-associated changes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-18T08%3A51%3A19IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Transcriptomic%20analysis%20of%20purified%20human%20cortical%20microglia%20reveals%20age-associated%20changes&rft.jtitle=Nature%20neuroscience&rft.au=Galatro,%20Thais%20F&rft.date=2017-08-01&rft.volume=20&rft.issue=8&rft.spage=1162&rft.epage=1171&rft.pages=1162-1171&rft.issn=1097-6256&rft.eissn=1546-1726&rft_id=info:doi/10.1038/nn.4597&rft_dat=%3Cgale_proqu%3EA499290064%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1946506720&rft_id=info:pmid/28671693&rft_galeid=A499290064&rfr_iscdi=true |