Single-cell RNA sequencing analysis of vestibular schwannoma reveals functionally distinct macrophage subsets
Background Vestibular schwannomas (VSs) remain a challenge due to their anatomical location and propensity to growth. Macrophages are present in VS but their roles in VS pathogenesis remains unknown. Objectives The objective was to assess phenotypic and functional profile of macrophages in VS with s...
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| Veröffentlicht in: | British journal of cancer 2024-06, Vol.130 (10), p.1659-1669 |
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| creator | Baruah, Paramita Mahony, Christopher Marshall, Jennifer L. Smith, Charlotte G. Monksfield, Peter Irving, Richard I. Dumitriu, Ingrid E. Buckley, Christopher D. Croft, Adam P. |
| description | Background
Vestibular schwannomas (VSs) remain a challenge due to their anatomical location and propensity to growth. Macrophages are present in VS but their roles in VS pathogenesis remains unknown.
Objectives
The objective was to assess phenotypic and functional profile of macrophages in VS with single-cell RNA sequencing (scRNAseq).
Methods
scRNAseq was carried out in three VS samples to examine characteristics of macrophages in the tumour. RT-qPCR was carried out on 10 VS samples for CD14, CD68 and CD163 and a panel of macrophage-associated molecules.
Results
scRNAseq revealed macrophages to be a major constituent of VS microenvironment with three distinct subclusters based on gene expression. The subclusters were also defined by expression of CD163, CD68 and IL-1β. AREG and PLAUR were expressed in the CD68+CD163+IL-1β+ subcluster, PLCG2 and NCKAP5 were expressed in CD68+CD163+IL-1β− subcluster and AUTS2 and SPP1 were expressed in the CD68+CD163−IL-1β+ subcluster. RT-qPCR showed expression of several macrophage markers in VS of which CD14, ALOX15, Interleukin-1β, INHBA and Colony Stimulating Factor-1R were found to have a high correlation with tumour volume.
Conclusions
Macrophages form an important component of VS stroma. scRNAseq reveals three distinct subsets of macrophages in the VS tissue which may have differing roles in the pathogenesis of VS. |
| doi_str_mv | 10.1038/s41416-024-02646-2 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11091088</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3054303310</sourcerecordid><originalsourceid>FETCH-LOGICAL-c426t-adc6c4ae8698536131cb393b4dd05dd284af491d285b2a9c08ee87fc450dd2b63</originalsourceid><addsrcrecordid>eNp9kUtv1DAUhS0EosPAH2CBLLFhE_A79gpVVaFIFUg81pbjODOuEnvwTaaaf4-HKeWxYGH5cb97bJ-D0HNKXlPC9RsQVFDVECbqUEI17AFaUclZQzVrH6IVIaRtiGHkDD0BuKlbQ3T7GJ1xLTQxXK7Q9CWmzRgaH8YRf_54jiF8X0Ly9RS75MYDRMB5wPsAc-yW0RUMfnvrUsqTwyXsgxsBD0vyc8yVHw-4jxWtezw5X_Ju6zYBw9JBmOEpejRUPjy7m9fo27vLrxdXzfWn9x8uzq8bL5iaG9d75YULWhktuaKc-o4b3om-J7LvmRZuEIbWheyYM57oEHQ7eCFJrXaKr9Hbk-5u6abQ-5Dm4ka7K3Fy5WCzi_bvSopbu8l7SykxlGhdFV7dKZRcDYHZThGOJrkU8gKWGdlSpSQ7oi__QW_yUqoXYDmRghPOa1xrxE5U9QSghOH-NZTYY5z2FKetcdqfcVpWm178-Y_7ll_5VYCfAKiltAnl993_kf0BQpet_Q</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3054303310</pqid></control><display><type>article</type><title>Single-cell RNA sequencing analysis of vestibular schwannoma reveals functionally distinct macrophage subsets</title><source>SpringerLink Journals - AutoHoldings</source><creator>Baruah, Paramita ; Mahony, Christopher ; Marshall, Jennifer L. ; Smith, Charlotte G. ; Monksfield, Peter ; Irving, Richard I. ; Dumitriu, Ingrid E. ; Buckley, Christopher D. ; Croft, Adam P.</creator><creatorcontrib>Baruah, Paramita ; Mahony, Christopher ; Marshall, Jennifer L. ; Smith, Charlotte G. ; Monksfield, Peter ; Irving, Richard I. ; Dumitriu, Ingrid E. ; Buckley, Christopher D. ; Croft, Adam P.</creatorcontrib><description>Background
Vestibular schwannomas (VSs) remain a challenge due to their anatomical location and propensity to growth. Macrophages are present in VS but their roles in VS pathogenesis remains unknown.
Objectives
The objective was to assess phenotypic and functional profile of macrophages in VS with single-cell RNA sequencing (scRNAseq).
Methods
scRNAseq was carried out in three VS samples to examine characteristics of macrophages in the tumour. RT-qPCR was carried out on 10 VS samples for CD14, CD68 and CD163 and a panel of macrophage-associated molecules.
Results
scRNAseq revealed macrophages to be a major constituent of VS microenvironment with three distinct subclusters based on gene expression. The subclusters were also defined by expression of CD163, CD68 and IL-1β. AREG and PLAUR were expressed in the CD68+CD163+IL-1β+ subcluster, PLCG2 and NCKAP5 were expressed in CD68+CD163+IL-1β− subcluster and AUTS2 and SPP1 were expressed in the CD68+CD163−IL-1β+ subcluster. RT-qPCR showed expression of several macrophage markers in VS of which CD14, ALOX15, Interleukin-1β, INHBA and Colony Stimulating Factor-1R were found to have a high correlation with tumour volume.
Conclusions
Macrophages form an important component of VS stroma. scRNAseq reveals three distinct subsets of macrophages in the VS tissue which may have differing roles in the pathogenesis of VS.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/s41416-024-02646-2</identifier><identifier>PMID: 38480935</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/250/580 ; 692/4028 ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; CD14 antigen ; CD163 antigen ; Colony-stimulating factor ; Drug Resistance ; Epidemiology ; Gene expression ; IL-1β ; Macrophages ; Microenvironments ; Molecular Medicine ; Oncology ; Pathogenesis ; Schwann cells ; Sequence analysis ; Stroma ; Tumors ; Vestibular system</subject><ispartof>British journal of cancer, 2024-06, Vol.130 (10), p.1659-1669</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c426t-adc6c4ae8698536131cb393b4dd05dd284af491d285b2a9c08ee87fc450dd2b63</cites><orcidid>0000-0001-6983-6381</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/s41416-024-02646-2$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41416-024-02646-2$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38480935$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Baruah, Paramita</creatorcontrib><creatorcontrib>Mahony, Christopher</creatorcontrib><creatorcontrib>Marshall, Jennifer L.</creatorcontrib><creatorcontrib>Smith, Charlotte G.</creatorcontrib><creatorcontrib>Monksfield, Peter</creatorcontrib><creatorcontrib>Irving, Richard I.</creatorcontrib><creatorcontrib>Dumitriu, Ingrid E.</creatorcontrib><creatorcontrib>Buckley, Christopher D.</creatorcontrib><creatorcontrib>Croft, Adam P.</creatorcontrib><title>Single-cell RNA sequencing analysis of vestibular schwannoma reveals functionally distinct macrophage subsets</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background
Vestibular schwannomas (VSs) remain a challenge due to their anatomical location and propensity to growth. Macrophages are present in VS but their roles in VS pathogenesis remains unknown.
Objectives
The objective was to assess phenotypic and functional profile of macrophages in VS with single-cell RNA sequencing (scRNAseq).
Methods
scRNAseq was carried out in three VS samples to examine characteristics of macrophages in the tumour. RT-qPCR was carried out on 10 VS samples for CD14, CD68 and CD163 and a panel of macrophage-associated molecules.
Results
scRNAseq revealed macrophages to be a major constituent of VS microenvironment with three distinct subclusters based on gene expression. The subclusters were also defined by expression of CD163, CD68 and IL-1β. AREG and PLAUR were expressed in the CD68+CD163+IL-1β+ subcluster, PLCG2 and NCKAP5 were expressed in CD68+CD163+IL-1β− subcluster and AUTS2 and SPP1 were expressed in the CD68+CD163−IL-1β+ subcluster. RT-qPCR showed expression of several macrophage markers in VS of which CD14, ALOX15, Interleukin-1β, INHBA and Colony Stimulating Factor-1R were found to have a high correlation with tumour volume.
Conclusions
Macrophages form an important component of VS stroma. scRNAseq reveals three distinct subsets of macrophages in the VS tissue which may have differing roles in the pathogenesis of VS.</description><subject>631/250/580</subject><subject>692/4028</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>CD14 antigen</subject><subject>CD163 antigen</subject><subject>Colony-stimulating factor</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Gene expression</subject><subject>IL-1β</subject><subject>Macrophages</subject><subject>Microenvironments</subject><subject>Molecular Medicine</subject><subject>Oncology</subject><subject>Pathogenesis</subject><subject>Schwann cells</subject><subject>Sequence analysis</subject><subject>Stroma</subject><subject>Tumors</subject><subject>Vestibular system</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><recordid>eNp9kUtv1DAUhS0EosPAH2CBLLFhE_A79gpVVaFIFUg81pbjODOuEnvwTaaaf4-HKeWxYGH5cb97bJ-D0HNKXlPC9RsQVFDVECbqUEI17AFaUclZQzVrH6IVIaRtiGHkDD0BuKlbQ3T7GJ1xLTQxXK7Q9CWmzRgaH8YRf_54jiF8X0Ly9RS75MYDRMB5wPsAc-yW0RUMfnvrUsqTwyXsgxsBD0vyc8yVHw-4jxWtezw5X_Ju6zYBw9JBmOEpejRUPjy7m9fo27vLrxdXzfWn9x8uzq8bL5iaG9d75YULWhktuaKc-o4b3om-J7LvmRZuEIbWheyYM57oEHQ7eCFJrXaKr9Hbk-5u6abQ-5Dm4ka7K3Fy5WCzi_bvSopbu8l7SykxlGhdFV7dKZRcDYHZThGOJrkU8gKWGdlSpSQ7oi__QW_yUqoXYDmRghPOa1xrxE5U9QSghOH-NZTYY5z2FKetcdqfcVpWm178-Y_7ll_5VYCfAKiltAnl993_kf0BQpet_Q</recordid><startdate>20240601</startdate><enddate>20240601</enddate><creator>Baruah, Paramita</creator><creator>Mahony, Christopher</creator><creator>Marshall, Jennifer L.</creator><creator>Smith, Charlotte G.</creator><creator>Monksfield, Peter</creator><creator>Irving, Richard I.</creator><creator>Dumitriu, Ingrid E.</creator><creator>Buckley, Christopher D.</creator><creator>Croft, Adam P.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6983-6381</orcidid></search><sort><creationdate>20240601</creationdate><title>Single-cell RNA sequencing analysis of vestibular schwannoma reveals functionally distinct macrophage subsets</title><author>Baruah, Paramita ; Mahony, Christopher ; Marshall, Jennifer L. ; Smith, Charlotte G. ; Monksfield, Peter ; Irving, Richard I. ; Dumitriu, Ingrid E. ; Buckley, Christopher D. ; Croft, Adam P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c426t-adc6c4ae8698536131cb393b4dd05dd284af491d285b2a9c08ee87fc450dd2b63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>631/250/580</topic><topic>692/4028</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>CD14 antigen</topic><topic>CD163 antigen</topic><topic>Colony-stimulating factor</topic><topic>Drug Resistance</topic><topic>Epidemiology</topic><topic>Gene expression</topic><topic>IL-1β</topic><topic>Macrophages</topic><topic>Microenvironments</topic><topic>Molecular Medicine</topic><topic>Oncology</topic><topic>Pathogenesis</topic><topic>Schwann cells</topic><topic>Sequence analysis</topic><topic>Stroma</topic><topic>Tumors</topic><topic>Vestibular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Baruah, Paramita</creatorcontrib><creatorcontrib>Mahony, Christopher</creatorcontrib><creatorcontrib>Marshall, Jennifer L.</creatorcontrib><creatorcontrib>Smith, Charlotte G.</creatorcontrib><creatorcontrib>Monksfield, Peter</creatorcontrib><creatorcontrib>Irving, Richard I.</creatorcontrib><creatorcontrib>Dumitriu, Ingrid E.</creatorcontrib><creatorcontrib>Buckley, Christopher D.</creatorcontrib><creatorcontrib>Croft, Adam P.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Baruah, Paramita</au><au>Mahony, Christopher</au><au>Marshall, Jennifer L.</au><au>Smith, Charlotte G.</au><au>Monksfield, Peter</au><au>Irving, Richard I.</au><au>Dumitriu, Ingrid E.</au><au>Buckley, Christopher D.</au><au>Croft, Adam P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Single-cell RNA sequencing analysis of vestibular schwannoma reveals functionally distinct macrophage subsets</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2024-06-01</date><risdate>2024</risdate><volume>130</volume><issue>10</issue><spage>1659</spage><epage>1669</epage><pages>1659-1669</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><abstract>Background
Vestibular schwannomas (VSs) remain a challenge due to their anatomical location and propensity to growth. Macrophages are present in VS but their roles in VS pathogenesis remains unknown.
Objectives
The objective was to assess phenotypic and functional profile of macrophages in VS with single-cell RNA sequencing (scRNAseq).
Methods
scRNAseq was carried out in three VS samples to examine characteristics of macrophages in the tumour. RT-qPCR was carried out on 10 VS samples for CD14, CD68 and CD163 and a panel of macrophage-associated molecules.
Results
scRNAseq revealed macrophages to be a major constituent of VS microenvironment with three distinct subclusters based on gene expression. The subclusters were also defined by expression of CD163, CD68 and IL-1β. AREG and PLAUR were expressed in the CD68+CD163+IL-1β+ subcluster, PLCG2 and NCKAP5 were expressed in CD68+CD163+IL-1β− subcluster and AUTS2 and SPP1 were expressed in the CD68+CD163−IL-1β+ subcluster. RT-qPCR showed expression of several macrophage markers in VS of which CD14, ALOX15, Interleukin-1β, INHBA and Colony Stimulating Factor-1R were found to have a high correlation with tumour volume.
Conclusions
Macrophages form an important component of VS stroma. scRNAseq reveals three distinct subsets of macrophages in the VS tissue which may have differing roles in the pathogenesis of VS.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>38480935</pmid><doi>10.1038/s41416-024-02646-2</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-6983-6381</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | British journal of cancer, 2024-06, Vol.130 (10), p.1659-1669 |
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| subjects | 631/250/580 692/4028 Biomedical and Life Sciences Biomedicine Cancer Research CD14 antigen CD163 antigen Colony-stimulating factor Drug Resistance Epidemiology Gene expression IL-1β Macrophages Microenvironments Molecular Medicine Oncology Pathogenesis Schwann cells Sequence analysis Stroma Tumors Vestibular system |
| title | Single-cell RNA sequencing analysis of vestibular schwannoma reveals functionally distinct macrophage subsets |
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