Single-cell sequencing of PIT1-positive pituitary adenoma highlights the pro-tumour microenvironment mediated by IFN-γ-induced tumour-associated fibroblasts remodelling
Background PIT1-positive pituitary adenoma (PIT1-PA) is one of the most important lineages of pituitary adenoma (PA), which causes systematic endocrine disorders and a worse prognosis. Tumour-associated fibroblast (TAF) is a crucial stroma cell type in the tumour microenvironment (TME). However, cel...
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| Veröffentlicht in: | British journal of cancer 2023-04, Vol.128 (6), p.1117-1133 |
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| creator | Lyu, Liang Jiang, Yong Ma, Weichao Li, Haiyan Liu, Xiaoling Li, Li Shen, Ao Yu, Yang Jiang, Shu Li, Huihui Zhou, Peizhi Yin, Senlin |
| description | Background
PIT1-positive pituitary adenoma (PIT1-PA) is one of the most important lineages of pituitary adenoma (PA), which causes systematic endocrine disorders and a worse prognosis. Tumour-associated fibroblast (TAF) is a crucial stroma cell type in the tumour microenvironment (TME). However, cellular and functional heterogeneity of TAF and immune cells in PIT1-PA have not been fully investigated.
Methods
By single-cell RNA sequencing of four PIT1-PAs and further analyses, we characterised the molecular and functional profiles of 28 different cell subtypes.
Results
PA stem cells in PIT1/SF1-positve PA were in a hybrid epithelial/mesenchymal state, and differentiated along the PIT1- and SF- dependent branches. C1Q was overwhelmingly expressed in tumour-associated macrophages, indicating its pro-tumoral functionality. PIT1-PA progression was characterised by lower cell–cell communication strength and higher cell adhesion-associated signals, indicating the immunosuppressive but pro-invasive microenvironment. IFN-γ signal repressed functional remodelling of myofibroblastic TAF (mTAF) towards inflammatory TAF/antigen-presenting TAF. IFN-γ inhibited mTAF phenotypes and N-cadherin expression through STAT3 signal axis. CDH2 knockdown in TAFs abrogated their pro-tumour function in PAs.
Conclusions
Our study builds up a cellular landscape of PIT1-PA TME and highlights anti-tumour function of IFN-γ mediated TAF remodelling, which benefits clinical treatments and drug development. |
| doi_str_mv | 10.1038/s41416-022-02126-5 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10006201</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2765070292</sourcerecordid><originalsourceid>FETCH-LOGICAL-c431t-7742bb18243f744d4883541fff552beb37fdc908a7244b22b7b169077f1f609e3</originalsourceid><addsrcrecordid>eNp9ks1u1DAUhS0EokPhBVggS2zYGPwbZ1YIVS2MVAESZW3ZiT3jKrEHOxmpj8Sa9-CZuENK-VmwsCLb3z059_gi9JTRl4yK9lWVTLKGUM5hMd4QdQ-tmBKcsJbr-2hFKdWErjk9QY9qvYbtmrb6IToRTSNYI9QKff0U03bwpPPDgKv_MvvUwQnOAX_cXDGyzzVO8eDxPk5znGy5wbb3KY8W7-J2N8CaKp52AJRMpnnMc8Fj7Er26RBLTqNPEx59H-3ke-xu8ObiPfn-jcTUzx2cLCXE1pq7hQnRlewGW0G4-DH3YA0sPUYPgh2qf3L7PUWfL86vzt6Ryw9vN2dvLkknBZuI1pI7BwFIEbSUvWxboSQLISjFnXdCh76DGKzmUjrOnXasWVOtAwsNXXtxil4vuvvZge8O_Bc7mH2JI3Rvso3m75sUd2abD4ZBvg2nDBRe3CqUDIHWyYyxHgO2yee5Gq4bRTXlaw7o83_Qa0gjQX9AtUpR1vAjxRcKYq21-HDnhlFzHAWzjIKBUTA_R8EoKHr2Zx93Jb_eHgCxABWu0taX3__-j-wP8qvD6Q</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2785501622</pqid></control><display><type>article</type><title>Single-cell sequencing of PIT1-positive pituitary adenoma highlights the pro-tumour microenvironment mediated by IFN-γ-induced tumour-associated fibroblasts remodelling</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Lyu, Liang ; Jiang, Yong ; Ma, Weichao ; Li, Haiyan ; Liu, Xiaoling ; Li, Li ; Shen, Ao ; Yu, Yang ; Jiang, Shu ; Li, Huihui ; Zhou, Peizhi ; Yin, Senlin</creator><creatorcontrib>Lyu, Liang ; Jiang, Yong ; Ma, Weichao ; Li, Haiyan ; Liu, Xiaoling ; Li, Li ; Shen, Ao ; Yu, Yang ; Jiang, Shu ; Li, Huihui ; Zhou, Peizhi ; Yin, Senlin</creatorcontrib><description>Background
PIT1-positive pituitary adenoma (PIT1-PA) is one of the most important lineages of pituitary adenoma (PA), which causes systematic endocrine disorders and a worse prognosis. Tumour-associated fibroblast (TAF) is a crucial stroma cell type in the tumour microenvironment (TME). However, cellular and functional heterogeneity of TAF and immune cells in PIT1-PA have not been fully investigated.
Methods
By single-cell RNA sequencing of four PIT1-PAs and further analyses, we characterised the molecular and functional profiles of 28 different cell subtypes.
Results
PA stem cells in PIT1/SF1-positve PA were in a hybrid epithelial/mesenchymal state, and differentiated along the PIT1- and SF- dependent branches. C1Q was overwhelmingly expressed in tumour-associated macrophages, indicating its pro-tumoral functionality. PIT1-PA progression was characterised by lower cell–cell communication strength and higher cell adhesion-associated signals, indicating the immunosuppressive but pro-invasive microenvironment. IFN-γ signal repressed functional remodelling of myofibroblastic TAF (mTAF) towards inflammatory TAF/antigen-presenting TAF. IFN-γ inhibited mTAF phenotypes and N-cadherin expression through STAT3 signal axis. CDH2 knockdown in TAFs abrogated their pro-tumour function in PAs.
Conclusions
Our study builds up a cellular landscape of PIT1-PA TME and highlights anti-tumour function of IFN-γ mediated TAF remodelling, which benefits clinical treatments and drug development.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/s41416-022-02126-5</identifier><identifier>PMID: 36631635</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67/1459/1740 ; 631/67/327 ; 692/4028/546 ; Adenoma ; Adenoma - genetics ; Biomedical and Life Sciences ; Biomedicine ; Cadherins ; Cancer Research ; Cancer-Associated Fibroblasts - metabolism ; Cell adhesion ; Cell interactions ; Drug development ; Drug Resistance ; Endocrine disorders ; Epidemiology ; Fibroblasts ; Fibroblasts - metabolism ; Humans ; Inflammation ; Interferon-gamma ; Macrophages ; Microenvironments ; Molecular Medicine ; N-Cadherin ; Oncology ; Phenotypes ; Pit1 protein ; Pituitary ; Pituitary Neoplasms - genetics ; Pituitary Neoplasms - metabolism ; Pituitary Neoplasms - pathology ; Stat3 protein ; Stroma ; Tumor Microenvironment ; Tumors ; γ-Interferon</subject><ispartof>British journal of cancer, 2023-04, Vol.128 (6), p.1117-1133</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2023. The Author(s), under exclusive licence to Springer Nature Limited.</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c431t-7742bb18243f744d4883541fff552beb37fdc908a7244b22b7b169077f1f609e3</citedby><cites>FETCH-LOGICAL-c431t-7742bb18243f744d4883541fff552beb37fdc908a7244b22b7b169077f1f609e3</cites><orcidid>0000-0003-2241-3749 ; 0000-0001-6004-3086 ; 0000-0001-9662-5838 ; 0000-0002-8017-5833</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10006201/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10006201/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36631635$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lyu, Liang</creatorcontrib><creatorcontrib>Jiang, Yong</creatorcontrib><creatorcontrib>Ma, Weichao</creatorcontrib><creatorcontrib>Li, Haiyan</creatorcontrib><creatorcontrib>Liu, Xiaoling</creatorcontrib><creatorcontrib>Li, Li</creatorcontrib><creatorcontrib>Shen, Ao</creatorcontrib><creatorcontrib>Yu, Yang</creatorcontrib><creatorcontrib>Jiang, Shu</creatorcontrib><creatorcontrib>Li, Huihui</creatorcontrib><creatorcontrib>Zhou, Peizhi</creatorcontrib><creatorcontrib>Yin, Senlin</creatorcontrib><title>Single-cell sequencing of PIT1-positive pituitary adenoma highlights the pro-tumour microenvironment mediated by IFN-γ-induced tumour-associated fibroblasts remodelling</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background
PIT1-positive pituitary adenoma (PIT1-PA) is one of the most important lineages of pituitary adenoma (PA), which causes systematic endocrine disorders and a worse prognosis. Tumour-associated fibroblast (TAF) is a crucial stroma cell type in the tumour microenvironment (TME). However, cellular and functional heterogeneity of TAF and immune cells in PIT1-PA have not been fully investigated.
Methods
By single-cell RNA sequencing of four PIT1-PAs and further analyses, we characterised the molecular and functional profiles of 28 different cell subtypes.
Results
PA stem cells in PIT1/SF1-positve PA were in a hybrid epithelial/mesenchymal state, and differentiated along the PIT1- and SF- dependent branches. C1Q was overwhelmingly expressed in tumour-associated macrophages, indicating its pro-tumoral functionality. PIT1-PA progression was characterised by lower cell–cell communication strength and higher cell adhesion-associated signals, indicating the immunosuppressive but pro-invasive microenvironment. IFN-γ signal repressed functional remodelling of myofibroblastic TAF (mTAF) towards inflammatory TAF/antigen-presenting TAF. IFN-γ inhibited mTAF phenotypes and N-cadherin expression through STAT3 signal axis. CDH2 knockdown in TAFs abrogated their pro-tumour function in PAs.
Conclusions
Our study builds up a cellular landscape of PIT1-PA TME and highlights anti-tumour function of IFN-γ mediated TAF remodelling, which benefits clinical treatments and drug development.</description><subject>631/67/1459/1740</subject><subject>631/67/327</subject><subject>692/4028/546</subject><subject>Adenoma</subject><subject>Adenoma - genetics</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cadherins</subject><subject>Cancer Research</subject><subject>Cancer-Associated Fibroblasts - metabolism</subject><subject>Cell adhesion</subject><subject>Cell interactions</subject><subject>Drug development</subject><subject>Drug Resistance</subject><subject>Endocrine disorders</subject><subject>Epidemiology</subject><subject>Fibroblasts</subject><subject>Fibroblasts - metabolism</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Interferon-gamma</subject><subject>Macrophages</subject><subject>Microenvironments</subject><subject>Molecular Medicine</subject><subject>N-Cadherin</subject><subject>Oncology</subject><subject>Phenotypes</subject><subject>Pit1 protein</subject><subject>Pituitary</subject><subject>Pituitary Neoplasms - genetics</subject><subject>Pituitary Neoplasms - metabolism</subject><subject>Pituitary Neoplasms - pathology</subject><subject>Stat3 protein</subject><subject>Stroma</subject><subject>Tumor Microenvironment</subject><subject>Tumors</subject><subject>γ-Interferon</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9ks1u1DAUhS0EokPhBVggS2zYGPwbZ1YIVS2MVAESZW3ZiT3jKrEHOxmpj8Sa9-CZuENK-VmwsCLb3z059_gi9JTRl4yK9lWVTLKGUM5hMd4QdQ-tmBKcsJbr-2hFKdWErjk9QY9qvYbtmrb6IToRTSNYI9QKff0U03bwpPPDgKv_MvvUwQnOAX_cXDGyzzVO8eDxPk5znGy5wbb3KY8W7-J2N8CaKp52AJRMpnnMc8Fj7Er26RBLTqNPEx59H-3ke-xu8ObiPfn-jcTUzx2cLCXE1pq7hQnRlewGW0G4-DH3YA0sPUYPgh2qf3L7PUWfL86vzt6Ryw9vN2dvLkknBZuI1pI7BwFIEbSUvWxboSQLISjFnXdCh76DGKzmUjrOnXasWVOtAwsNXXtxil4vuvvZge8O_Bc7mH2JI3Rvso3m75sUd2abD4ZBvg2nDBRe3CqUDIHWyYyxHgO2yee5Gq4bRTXlaw7o83_Qa0gjQX9AtUpR1vAjxRcKYq21-HDnhlFzHAWzjIKBUTA_R8EoKHr2Zx93Jb_eHgCxABWu0taX3__-j-wP8qvD6Q</recordid><startdate>20230406</startdate><enddate>20230406</enddate><creator>Lyu, Liang</creator><creator>Jiang, Yong</creator><creator>Ma, Weichao</creator><creator>Li, Haiyan</creator><creator>Liu, Xiaoling</creator><creator>Li, Li</creator><creator>Shen, Ao</creator><creator>Yu, Yang</creator><creator>Jiang, Shu</creator><creator>Li, Huihui</creator><creator>Zhou, Peizhi</creator><creator>Yin, Senlin</creator><general>Nature Publishing Group UK</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>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2241-3749</orcidid><orcidid>https://orcid.org/0000-0001-6004-3086</orcidid><orcidid>https://orcid.org/0000-0001-9662-5838</orcidid><orcidid>https://orcid.org/0000-0002-8017-5833</orcidid></search><sort><creationdate>20230406</creationdate><title>Single-cell sequencing of PIT1-positive pituitary adenoma highlights the pro-tumour microenvironment mediated by IFN-γ-induced tumour-associated fibroblasts remodelling</title><author>Lyu, Liang ; Jiang, Yong ; Ma, Weichao ; Li, Haiyan ; Liu, Xiaoling ; Li, Li ; Shen, Ao ; Yu, Yang ; Jiang, Shu ; Li, Huihui ; Zhou, Peizhi ; Yin, Senlin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c431t-7742bb18243f744d4883541fff552beb37fdc908a7244b22b7b169077f1f609e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>631/67/1459/1740</topic><topic>631/67/327</topic><topic>692/4028/546</topic><topic>Adenoma</topic><topic>Adenoma - genetics</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cadherins</topic><topic>Cancer Research</topic><topic>Cancer-Associated Fibroblasts - metabolism</topic><topic>Cell adhesion</topic><topic>Cell interactions</topic><topic>Drug development</topic><topic>Drug Resistance</topic><topic>Endocrine disorders</topic><topic>Epidemiology</topic><topic>Fibroblasts</topic><topic>Fibroblasts - metabolism</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Interferon-gamma</topic><topic>Macrophages</topic><topic>Microenvironments</topic><topic>Molecular Medicine</topic><topic>N-Cadherin</topic><topic>Oncology</topic><topic>Phenotypes</topic><topic>Pit1 protein</topic><topic>Pituitary</topic><topic>Pituitary Neoplasms - genetics</topic><topic>Pituitary Neoplasms - metabolism</topic><topic>Pituitary Neoplasms - pathology</topic><topic>Stat3 protein</topic><topic>Stroma</topic><topic>Tumor Microenvironment</topic><topic>Tumors</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lyu, Liang</creatorcontrib><creatorcontrib>Jiang, Yong</creatorcontrib><creatorcontrib>Ma, Weichao</creatorcontrib><creatorcontrib>Li, Haiyan</creatorcontrib><creatorcontrib>Liu, Xiaoling</creatorcontrib><creatorcontrib>Li, Li</creatorcontrib><creatorcontrib>Shen, Ao</creatorcontrib><creatorcontrib>Yu, Yang</creatorcontrib><creatorcontrib>Jiang, Shu</creatorcontrib><creatorcontrib>Li, Huihui</creatorcontrib><creatorcontrib>Zhou, Peizhi</creatorcontrib><creatorcontrib>Yin, Senlin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</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>Lyu, Liang</au><au>Jiang, Yong</au><au>Ma, Weichao</au><au>Li, Haiyan</au><au>Liu, Xiaoling</au><au>Li, Li</au><au>Shen, Ao</au><au>Yu, Yang</au><au>Jiang, Shu</au><au>Li, Huihui</au><au>Zhou, Peizhi</au><au>Yin, Senlin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Single-cell sequencing of PIT1-positive pituitary adenoma highlights the pro-tumour microenvironment mediated by IFN-γ-induced tumour-associated fibroblasts remodelling</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2023-04-06</date><risdate>2023</risdate><volume>128</volume><issue>6</issue><spage>1117</spage><epage>1133</epage><pages>1117-1133</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><abstract>Background
PIT1-positive pituitary adenoma (PIT1-PA) is one of the most important lineages of pituitary adenoma (PA), which causes systematic endocrine disorders and a worse prognosis. Tumour-associated fibroblast (TAF) is a crucial stroma cell type in the tumour microenvironment (TME). However, cellular and functional heterogeneity of TAF and immune cells in PIT1-PA have not been fully investigated.
Methods
By single-cell RNA sequencing of four PIT1-PAs and further analyses, we characterised the molecular and functional profiles of 28 different cell subtypes.
Results
PA stem cells in PIT1/SF1-positve PA were in a hybrid epithelial/mesenchymal state, and differentiated along the PIT1- and SF- dependent branches. C1Q was overwhelmingly expressed in tumour-associated macrophages, indicating its pro-tumoral functionality. PIT1-PA progression was characterised by lower cell–cell communication strength and higher cell adhesion-associated signals, indicating the immunosuppressive but pro-invasive microenvironment. IFN-γ signal repressed functional remodelling of myofibroblastic TAF (mTAF) towards inflammatory TAF/antigen-presenting TAF. IFN-γ inhibited mTAF phenotypes and N-cadherin expression through STAT3 signal axis. CDH2 knockdown in TAFs abrogated their pro-tumour function in PAs.
Conclusions
Our study builds up a cellular landscape of PIT1-PA TME and highlights anti-tumour function of IFN-γ mediated TAF remodelling, which benefits clinical treatments and drug development.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>36631635</pmid><doi>10.1038/s41416-022-02126-5</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0003-2241-3749</orcidid><orcidid>https://orcid.org/0000-0001-6004-3086</orcidid><orcidid>https://orcid.org/0000-0001-9662-5838</orcidid><orcidid>https://orcid.org/0000-0002-8017-5833</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| source | MEDLINE; Springer Nature - Complete Springer Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | 631/67/1459/1740 631/67/327 692/4028/546 Adenoma Adenoma - genetics Biomedical and Life Sciences Biomedicine Cadherins Cancer Research Cancer-Associated Fibroblasts - metabolism Cell adhesion Cell interactions Drug development Drug Resistance Endocrine disorders Epidemiology Fibroblasts Fibroblasts - metabolism Humans Inflammation Interferon-gamma Macrophages Microenvironments Molecular Medicine N-Cadherin Oncology Phenotypes Pit1 protein Pituitary Pituitary Neoplasms - genetics Pituitary Neoplasms - metabolism Pituitary Neoplasms - pathology Stat3 protein Stroma Tumor Microenvironment Tumors γ-Interferon |
| title | Single-cell sequencing of PIT1-positive pituitary adenoma highlights the pro-tumour microenvironment mediated by IFN-γ-induced tumour-associated fibroblasts remodelling |
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