Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry
Microglia, the specialized innate immune cells of the CNS, play crucial roles in neural development and function. Different phenotypes and functions have been ascribed to rodent microglia, but little is known about human microglia (huMG) heterogeneity. Difficulties in procuring huMG and their suscep...
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| Veröffentlicht in: | Nature neuroscience 2019-01, Vol.22 (1), p.78-90 |
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| creator | Böttcher, Chotima Schlickeiser, Stephan Sneeboer, Marjolein A. M. Kunkel, Desiree Knop, Anniki Paza, Evdokia Fidzinski, Pawel Kraus, Larissa Snijders, Gijsje J. L. Kahn, René S Schulz, Axel R Mei, Henrik E Hol, Elly M. Siegmund, Britta Glauben, Rainer Spruth, Eike J de Witte, Lot D Priller, Josef |
| description | Microglia, the specialized innate immune cells of the CNS, play crucial roles in neural development and function. Different phenotypes and functions have been ascribed to rodent microglia, but little is known about human microglia (huMG) heterogeneity. Difficulties in procuring huMG and their susceptibility to cryopreservation damage have limited large-scale studies. Here we applied multiplexed mass cytometry for a comprehensive characterization of postmortem huMG (10
3
– 10
4
cells). We determined expression levels of 57 markers on huMG isolated from up to five different brain regions of nine donors. We identified the phenotypic signature of huMG, which was distinct from peripheral myeloid cells but was comparable to fresh huMG. We detected microglia regional heterogeneity using a hybrid workflow combining Cytobank and R/Bioconductor for multidimensional data analysis. Together, these methodologies allowed us to perform high-dimensional, large-scale immunophenotyping of huMG at the single-cell level, which facilitates their unambiguous profiling in health and disease.
Single-cell mass cytometry was applied to comprehensively characterize postmortem and fresh human microglia. Using a hybrid workflow for multidimensional data analysis, a core signature and regional heterogeneity were identified. |
| doi_str_mv | 10.1038/s41593-018-0290-2 |
| format | Article |
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3
– 10
4
cells). We determined expression levels of 57 markers on huMG isolated from up to five different brain regions of nine donors. We identified the phenotypic signature of huMG, which was distinct from peripheral myeloid cells but was comparable to fresh huMG. We detected microglia regional heterogeneity using a hybrid workflow combining Cytobank and R/Bioconductor for multidimensional data analysis. Together, these methodologies allowed us to perform high-dimensional, large-scale immunophenotyping of huMG at the single-cell level, which facilitates their unambiguous profiling in health and disease.
Single-cell mass cytometry was applied to comprehensively characterize postmortem and fresh human microglia. Using a hybrid workflow for multidimensional data analysis, a core signature and regional heterogeneity were identified.</description><identifier>ISSN: 1097-6256</identifier><identifier>EISSN: 1546-1726</identifier><identifier>DOI: 10.1038/s41593-018-0290-2</identifier><identifier>PMID: 30559476</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/378/2596/1953 ; 631/378/371 ; Animal Genetics and Genomics ; Behavioral Sciences ; Biological Techniques ; Biomedical and Life Sciences ; Biomedicine ; Brain ; Brain - cytology ; Brain - metabolism ; Central nervous system ; Composition ; Criminal investigation ; Cryopreservation ; Cytometry ; Data analysis ; Data processing ; Female ; Health aspects ; Heterogeneity ; Humans ; Identification and classification ; Immune system ; Immunophenotyping ; Information management ; Lectins, C-Type - metabolism ; Male ; Mannose Receptor ; Mannose-Binding Lectins - metabolism ; Microglia ; Microglia - cytology ; Microglia - metabolism ; Multidimensional data ; Multiplexing ; Myeloid cells ; Myeloid Cells - cytology ; Myeloid Cells - metabolism ; Neurobiology ; Neurosciences ; Online analytical processing ; Phenotype ; Phenotypes ; Physiological aspects ; Receptors, Cell Surface - metabolism ; Workflow ; Workflow software</subject><ispartof>Nature neuroscience, 2019-01, Vol.22 (1), p.78-90</ispartof><rights>The Author(s), under exclusive licence to Springer Nature America, Inc. 2018</rights><rights>COPYRIGHT 2019 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jan 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c473t-4978a26558d1c531cb49e36bcc276b88e65892c3e43e2607dece9eeebae08fb53</citedby><cites>FETCH-LOGICAL-c473t-4978a26558d1c531cb49e36bcc276b88e65892c3e43e2607dece9eeebae08fb53</cites><orcidid>0000-0001-7596-0979 ; 0000-0002-5106-0148 ; 0000-0001-8994-606X ; 0000-0001-5604-2603 ; 0000-0002-6226-586X ; 0000-0002-4297-8598</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/s41593-018-0290-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41593-018-0290-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30559476$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Böttcher, Chotima</creatorcontrib><creatorcontrib>Schlickeiser, Stephan</creatorcontrib><creatorcontrib>Sneeboer, Marjolein A. M.</creatorcontrib><creatorcontrib>Kunkel, Desiree</creatorcontrib><creatorcontrib>Knop, Anniki</creatorcontrib><creatorcontrib>Paza, Evdokia</creatorcontrib><creatorcontrib>Fidzinski, Pawel</creatorcontrib><creatorcontrib>Kraus, Larissa</creatorcontrib><creatorcontrib>Snijders, Gijsje J. L.</creatorcontrib><creatorcontrib>Kahn, René S</creatorcontrib><creatorcontrib>Schulz, Axel R</creatorcontrib><creatorcontrib>Mei, Henrik E</creatorcontrib><creatorcontrib>Hol, Elly M.</creatorcontrib><creatorcontrib>Siegmund, Britta</creatorcontrib><creatorcontrib>Glauben, Rainer</creatorcontrib><creatorcontrib>Spruth, Eike J</creatorcontrib><creatorcontrib>de Witte, Lot D</creatorcontrib><creatorcontrib>Priller, Josef</creatorcontrib><creatorcontrib>NBB-Psy</creatorcontrib><title>Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry</title><title>Nature neuroscience</title><addtitle>Nat Neurosci</addtitle><addtitle>Nat Neurosci</addtitle><description>Microglia, the specialized innate immune cells of the CNS, play crucial roles in neural development and function. Different phenotypes and functions have been ascribed to rodent microglia, but little is known about human microglia (huMG) heterogeneity. Difficulties in procuring huMG and their susceptibility to cryopreservation damage have limited large-scale studies. Here we applied multiplexed mass cytometry for a comprehensive characterization of postmortem huMG (10
3
– 10
4
cells). We determined expression levels of 57 markers on huMG isolated from up to five different brain regions of nine donors. We identified the phenotypic signature of huMG, which was distinct from peripheral myeloid cells but was comparable to fresh huMG. We detected microglia regional heterogeneity using a hybrid workflow combining Cytobank and R/Bioconductor for multidimensional data analysis. Together, these methodologies allowed us to perform high-dimensional, large-scale immunophenotyping of huMG at the single-cell level, which facilitates their unambiguous profiling in health and disease.
Single-cell mass cytometry was applied to comprehensively characterize postmortem and fresh human microglia. Using a hybrid workflow for multidimensional data analysis, a core signature and regional heterogeneity were identified.</description><subject>631/378/2596/1953</subject><subject>631/378/371</subject><subject>Animal Genetics and Genomics</subject><subject>Behavioral Sciences</subject><subject>Biological Techniques</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain</subject><subject>Brain - cytology</subject><subject>Brain - metabolism</subject><subject>Central nervous system</subject><subject>Composition</subject><subject>Criminal investigation</subject><subject>Cryopreservation</subject><subject>Cytometry</subject><subject>Data analysis</subject><subject>Data processing</subject><subject>Female</subject><subject>Health aspects</subject><subject>Heterogeneity</subject><subject>Humans</subject><subject>Identification and classification</subject><subject>Immune system</subject><subject>Immunophenotyping</subject><subject>Information management</subject><subject>Lectins, C-Type - metabolism</subject><subject>Male</subject><subject>Mannose Receptor</subject><subject>Mannose-Binding Lectins - metabolism</subject><subject>Microglia</subject><subject>Microglia - cytology</subject><subject>Microglia - metabolism</subject><subject>Multidimensional data</subject><subject>Multiplexing</subject><subject>Myeloid cells</subject><subject>Myeloid Cells - cytology</subject><subject>Myeloid Cells - metabolism</subject><subject>Neurobiology</subject><subject>Neurosciences</subject><subject>Online analytical processing</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Physiological aspects</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>Workflow</subject><subject>Workflow software</subject><issn>1097-6256</issn><issn>1546-1726</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kstu1TAQhiMEoqXwAGyQJTawSPH9sqwqoJUqIXFZW44zSX2UOIfYkZq3r8MpVAeBvLA98_0j_56pqtcEnxPM9IfEiTCsxkTXmBpc0yfVKRFc1kRR-bScsVG1pEKeVC9S2mGMldDmeXXCsBCGK3la7a6W0UU0Bj9P_RAcmqEPU3QDuoUMJQYRQl6Riy3a30Kc8rqHhNotOYYILWpWNC5DDvsB7so1hdgPUHsYBjS6lJBf8zRCnteX1bPODQlePexn1Y9PH79fXtU3Xz5fX17c1J4rlmtulHZUCqFb4gUjvuEGmGy8p0o2WoMsHqhnwBlQiVULHgwANA6w7hrBzqp3h7r7efq5QMp2DGl7j4swLclSIjTlinJT0Ld_obtpmYv7X5TSUhiFH6neDWBD7KY8O78VtRdCMcaM4qRQ5_-gymqh_O4UoQslfiR4fyQoTIa73LslJXv97esxSw5saVNKM3R2P4fRzasl2G6zYA-zYMss2G0WLC2aNw_mlmaE9o_id_MLQA9AKqnYw_zo_v9V7wGPWr5W</recordid><startdate>20190101</startdate><enddate>20190101</enddate><creator>Böttcher, Chotima</creator><creator>Schlickeiser, Stephan</creator><creator>Sneeboer, Marjolein A. 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L.</creator><creator>Kahn, René S</creator><creator>Schulz, Axel R</creator><creator>Mei, Henrik E</creator><creator>Hol, Elly M.</creator><creator>Siegmund, Britta</creator><creator>Glauben, Rainer</creator><creator>Spruth, Eike J</creator><creator>de Witte, Lot D</creator><creator>Priller, Josef</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7596-0979</orcidid><orcidid>https://orcid.org/0000-0002-5106-0148</orcidid><orcidid>https://orcid.org/0000-0001-8994-606X</orcidid><orcidid>https://orcid.org/0000-0001-5604-2603</orcidid><orcidid>https://orcid.org/0000-0002-6226-586X</orcidid><orcidid>https://orcid.org/0000-0002-4297-8598</orcidid></search><sort><creationdate>20190101</creationdate><title>Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry</title><author>Böttcher, Chotima ; Schlickeiser, Stephan ; Sneeboer, Marjolein A. M. ; Kunkel, Desiree ; Knop, Anniki ; Paza, Evdokia ; Fidzinski, Pawel ; Kraus, Larissa ; Snijders, Gijsje J. L. ; Kahn, René S ; Schulz, Axel R ; Mei, Henrik E ; Hol, Elly M. ; Siegmund, Britta ; Glauben, Rainer ; Spruth, Eike J ; de Witte, Lot D ; Priller, Josef</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c473t-4978a26558d1c531cb49e36bcc276b88e65892c3e43e2607dece9eeebae08fb53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>631/378/2596/1953</topic><topic>631/378/371</topic><topic>Animal Genetics and Genomics</topic><topic>Behavioral Sciences</topic><topic>Biological Techniques</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain</topic><topic>Brain - cytology</topic><topic>Brain - metabolism</topic><topic>Central nervous system</topic><topic>Composition</topic><topic>Criminal investigation</topic><topic>Cryopreservation</topic><topic>Cytometry</topic><topic>Data analysis</topic><topic>Data processing</topic><topic>Female</topic><topic>Health aspects</topic><topic>Heterogeneity</topic><topic>Humans</topic><topic>Identification and classification</topic><topic>Immune system</topic><topic>Immunophenotyping</topic><topic>Information management</topic><topic>Lectins, C-Type - metabolism</topic><topic>Male</topic><topic>Mannose Receptor</topic><topic>Mannose-Binding Lectins - metabolism</topic><topic>Microglia</topic><topic>Microglia - cytology</topic><topic>Microglia - metabolism</topic><topic>Multidimensional data</topic><topic>Multiplexing</topic><topic>Myeloid cells</topic><topic>Myeloid Cells - cytology</topic><topic>Myeloid Cells - metabolism</topic><topic>Neurobiology</topic><topic>Neurosciences</topic><topic>Online analytical processing</topic><topic>Phenotype</topic><topic>Phenotypes</topic><topic>Physiological aspects</topic><topic>Receptors, Cell Surface - metabolism</topic><topic>Workflow</topic><topic>Workflow software</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Böttcher, Chotima</creatorcontrib><creatorcontrib>Schlickeiser, Stephan</creatorcontrib><creatorcontrib>Sneeboer, Marjolein A. 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M.</au><au>Kunkel, Desiree</au><au>Knop, Anniki</au><au>Paza, Evdokia</au><au>Fidzinski, Pawel</au><au>Kraus, Larissa</au><au>Snijders, Gijsje J. L.</au><au>Kahn, René S</au><au>Schulz, Axel R</au><au>Mei, Henrik E</au><au>Hol, Elly M.</au><au>Siegmund, Britta</au><au>Glauben, Rainer</au><au>Spruth, Eike J</au><au>de Witte, Lot D</au><au>Priller, Josef</au><aucorp>NBB-Psy</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry</atitle><jtitle>Nature neuroscience</jtitle><stitle>Nat Neurosci</stitle><addtitle>Nat Neurosci</addtitle><date>2019-01-01</date><risdate>2019</risdate><volume>22</volume><issue>1</issue><spage>78</spage><epage>90</epage><pages>78-90</pages><issn>1097-6256</issn><eissn>1546-1726</eissn><abstract>Microglia, the specialized innate immune cells of the CNS, play crucial roles in neural development and function. Different phenotypes and functions have been ascribed to rodent microglia, but little is known about human microglia (huMG) heterogeneity. Difficulties in procuring huMG and their susceptibility to cryopreservation damage have limited large-scale studies. Here we applied multiplexed mass cytometry for a comprehensive characterization of postmortem huMG (10
3
– 10
4
cells). We determined expression levels of 57 markers on huMG isolated from up to five different brain regions of nine donors. We identified the phenotypic signature of huMG, which was distinct from peripheral myeloid cells but was comparable to fresh huMG. We detected microglia regional heterogeneity using a hybrid workflow combining Cytobank and R/Bioconductor for multidimensional data analysis. Together, these methodologies allowed us to perform high-dimensional, large-scale immunophenotyping of huMG at the single-cell level, which facilitates their unambiguous profiling in health and disease.
Single-cell mass cytometry was applied to comprehensively characterize postmortem and fresh human microglia. Using a hybrid workflow for multidimensional data analysis, a core signature and regional heterogeneity were identified.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>30559476</pmid><doi>10.1038/s41593-018-0290-2</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-7596-0979</orcidid><orcidid>https://orcid.org/0000-0002-5106-0148</orcidid><orcidid>https://orcid.org/0000-0001-8994-606X</orcidid><orcidid>https://orcid.org/0000-0001-5604-2603</orcidid><orcidid>https://orcid.org/0000-0002-6226-586X</orcidid><orcidid>https://orcid.org/0000-0002-4297-8598</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1097-6256 |
| ispartof | Nature neuroscience, 2019-01, Vol.22 (1), p.78-90 |
| issn | 1097-6256 1546-1726 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2158247249 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online |
| subjects | 631/378/2596/1953 631/378/371 Animal Genetics and Genomics Behavioral Sciences Biological Techniques Biomedical and Life Sciences Biomedicine Brain Brain - cytology Brain - metabolism Central nervous system Composition Criminal investigation Cryopreservation Cytometry Data analysis Data processing Female Health aspects Heterogeneity Humans Identification and classification Immune system Immunophenotyping Information management Lectins, C-Type - metabolism Male Mannose Receptor Mannose-Binding Lectins - metabolism Microglia Microglia - cytology Microglia - metabolism Multidimensional data Multiplexing Myeloid cells Myeloid Cells - cytology Myeloid Cells - metabolism Neurobiology Neurosciences Online analytical processing Phenotype Phenotypes Physiological aspects Receptors, Cell Surface - metabolism Workflow Workflow software |
| title | Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-14T09%3A16%3A47IST&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=Human%20microglia%20regional%20heterogeneity%20and%20phenotypes%20determined%20by%20multiplexed%20single-cell%20mass%20cytometry&rft.jtitle=Nature%20neuroscience&rft.au=B%C3%B6ttcher,%20Chotima&rft.aucorp=NBB-Psy&rft.date=2019-01-01&rft.volume=22&rft.issue=1&rft.spage=78&rft.epage=90&rft.pages=78-90&rft.issn=1097-6256&rft.eissn=1546-1726&rft_id=info:doi/10.1038/s41593-018-0290-2&rft_dat=%3Cgale_proqu%3EA573339741%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=2157865970&rft_id=info:pmid/30559476&rft_galeid=A573339741&rfr_iscdi=true |