{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T18:29:49Z","timestamp":1786386589688,"version":"build-2736575974"},"reference-count":59,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2026,8,11]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>The Cre\/loxP recombination system is the main tool for cell type\u2013specific lineage tracing and gene targeting. Currently available smooth muscle cell (SMC)\u2013specific Cre mouse lines show off-target activity outside the SMC lineage and are unable to distinguish among arterial SMCs (ASMCs), venous SMCs, and nonvascular SMCs (NVSMCs). These limitations prevent ASMC- and NVSMC-specific gene targeting, which is required to characterize the role of SMCs in different organs and diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      To achieve precise manipulation of ASMCs in vivo, we combined alleles for\n                      <jats:italic toggle=\"yes\">Cspg4-Dre<\/jats:italic>\n                      and rox-Stop\u2013containing\n                      <jats:italic toggle=\"yes\">Acta2-CreER<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">Acta2-rox-CreER<\/jats:italic>\n                      ), generating a mouse line with Cre activity exclusively in ASMCs. RNA sequencing of fluorescence-activated cell sorting\u2013isolated ASMCs was used to reveal differences in ASMCs among multiple organs. To specifically target and characterize NVSMCs in different organs, a combination of\n                      <jats:italic toggle=\"yes\">Chrm2-Dre<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Acta2-rox-CreER<\/jats:italic>\n                      was used. Disease-specific transcriptional changes of pulmonary ASMCs and NVSMCs were determined in the Sugen 5416\/hypoxia model of pulmonary arterial hypertension. Usefulness for functional studies was assessed by inactivation of the genes for the splicing factors RBPMS (RNA-binding protein with multiple splicing) and RBPMS2 (RNA-binding protein with multiple splicing 2) in ASMCs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Intersectional genetic approaches using\n                      <jats:italic toggle=\"yes\">Cspg4-Dre<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Acta2-rox-CreER<\/jats:italic>\n                      mouse lines specifically targeted ASMCs within various organs. A combination of\n                      <jats:italic toggle=\"yes\">Chrm2-Dre<\/jats:italic>\n                      with\n                      <jats:italic toggle=\"yes\">Acta2-rox-CreER<\/jats:italic>\n                      achieved specific targeting of NVSMCs. Transcriptomic profiling revealed distinct gene expression signatures in ASMCs of different organs, indicating organ-dependent transcriptional adaptation of ASMCs. Transcriptional differences among NVSMCs were found in the lung, intestine, and bladder. Activation of distinct pathways was uncovered in pulmonary ASMCs and bronchial SMCs after induction of pulmonary arterial hypertension. Inactivation of\n                      <jats:italic toggle=\"yes\">Rbpms<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Rbpms2<\/jats:italic>\n                      in ASMCs increased thickness of the muscular layer in pulmonary arteries, whereas inactivation in all SMCs abolished the contractile phenotype of NVSMCs in the intestine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>The successful generation of mouse lines specifically targeting different subtypes of SMCs enhances specificity, allowing distinction between vascular and nonvascular effects of diseased SMCs. The identification of vessel bed\u2013specific gene signatures will pave the way for specific manipulation of SMCs in distinct diseased organs, such as the lung in pulmonary arterial hypertension.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.125.076318","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T09:00:18Z","timestamp":1776070818000},"page":"565-583","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Cell Type\u2013Specific Targeting of Different Smooth Muscle Cell Populations by Intersectional Genetics"],"prefix":"10.1161","volume":"154","author":[{"given":"Lei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (L.W., M.S., S.G., C.K., J.D., A.S., 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Lung Center (E.E.A., S.B.)."},{"name":"Institute for Lung Health, Justus-Liebig-University Giessen, Germany (E.E.A., S.B., T.B.)."},{"name":"German Center for Lung Research (DZL), Giessen, Germany (E.E.A., S.B., T.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5987-4579","authenticated-orcid":true,"given":"Saverio","family":"Bellusci","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Pulmonology), Universities of Giessen and Marburg Lung Center (E.E.A., S.B.)."},{"name":"Institute for Lung Health, Justus-Liebig-University Giessen, Germany (E.E.A., S.B., T.B.)."},{"name":"German Center for Lung Research (DZL), Giessen, Germany (E.E.A., S.B., T.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8013-5906","authenticated-orcid":true,"given":"Carsten","family":"Kuenne","sequence":"additional","affiliation":[{"name":"Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (L.W., M.S., S.G., C.K., J.D., A.S., T.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhua","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (L.W., M.S., S.G., C.K., J.D., A.S., T.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2715-8345","authenticated-orcid":true,"given":"Andre","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (L.W., M.S., S.G., C.K., J.D., A.S., 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