Pericyte Progenitor Coupling to the Emerging Endothelium during Vasculogenesis via Connexin43

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dc.contributor.authorPayne, Laura Bethen
dc.contributor.authorTewari, Bhanu P.en
dc.contributor.authorDunkenberger, Loganen
dc.contributor.authorBond, Samanthaen
dc.contributor.authorSavelli, Alyssaen
dc.contributor.authorDarden, Jordanen
dc.contributor.authorZhao, Huaningen
dc.contributor.authorWilli, Carolineen
dc.contributor.authorKanodia, Ronaken
dc.contributor.authorGude, Rosalieen
dc.contributor.authorPowell, Michael D.en
dc.contributor.authorOestreich, Kenneth J.en
dc.contributor.authorSontheimer, Haralden
dc.contributor.authorDal-Pra, Sophieen
dc.contributor.authorChappell, John C.en
dc.date.accessioned2023-09-26T14:58:48Zen
dc.date.available2023-09-26T14:58:48Zen
dc.date.issued2022-04-01en
dc.date.updated2023-09-26T14:55:13Zen
dc.description.abstractBackground: Vascular pericytes stabilize blood vessels and contribute to their maturation, while playing other key roles in microvascular function. Nevertheless, relatively little is known about involvement of their precursors in the earliest stages of vascular development, specifically during vasculogenesis. Methods: We combined high-power, time-lapse imaging with transcriptional profiling of emerging pericytes and endothelial cells in reporter mouse and cell lines. We also analyzed conditional transgenic animals deficient in Cx43/Gja1 (connexin 43/gap junction alpha-1) expression within Ng2+ cells. Results: A subset of Ng2-DsRed+ cells, likely pericyte/mural cell precursors, arose alongside endothelial cell differentiation and organization and physically engaged vasculogenic endothelium in vivo and in vitro. We found no overlap between this population of differentiating pericyte/mural progenitors and other lineages including hemangiogenic and neuronal/glial cell types. We also observed cell-cell coupling and identified Cx43-based gap junctions contributing to pericyte-endothelial cell precursor communication during vascular assembly. Genetic loss of Cx43/Gja1 in Ng2+ pericyte progenitors compromised embryonic blood vessel formation in a subset of animals, while surviving mutants displayed little-to-no vessel abnormalities, suggesting a resilience to Cx43/Gja1 loss in Ng2+ cells or potential compensation by additional connexin isoforms. Conclusions: Together, our data suggest that a distinct pericyte lineage emerges alongside vasculogenesis and directly communicates with the nascent endothelium via Cx43 during early vessel formation. Cx43/Gja1 loss in pericyte/mural cell progenitors can induce embryonic vessel dysmorphogenesis, but alternate connexin isoforms may be able to compensate. These data provide insight that may reshape the current framework of vascular development and may also inform tissue revascularization/vascularization strategies.en
dc.description.versionAccepted versionen
dc.format.extentPages E96-E114en
dc.format.extent19 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1161/ATVBAHA.121.317324en
dc.identifier.eissn1524-4636en
dc.identifier.issn1079-5642en
dc.identifier.issue4en
dc.identifier.orcidChappell, John [0000-0002-0427-5170]en
dc.identifier.pmid35139658en
dc.identifier.urihttp://hdl.handle.net/10919/116337en
dc.identifier.volume42en
dc.language.isoenen
dc.publisherLippincott Williams & Wilkinsen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectHematologyen
dc.subjectPeripheral Vascular Diseaseen
dc.subjectCardiovascular System & Cardiologyen
dc.subjectconnexin 43en
dc.subjectembryonic stem cellsen
dc.subjectendothelial cellsen
dc.subjectgap junctionsen
dc.subjectpericytesen
dc.subjectEMBRYONIC STEM-CELLSen
dc.subjectSMOOTH-MUSCLE-CELLSen
dc.subjectBASEMENT-MEMBRANEen
dc.subjectNEURAL CRESTen
dc.subjectVASCULAR DEVELOPMENTen
dc.subjectDOWN-REGULATIONen
dc.subjectBLOOD-VESSELSen
dc.subjectEXPRESSIONen
dc.subjectJUNCTIONen
dc.subjectDIFFERENTIATIONen
dc.subject3208 Medical Physiologyen
dc.subject32 Biomedical and Clinical Sciencesen
dc.subjectStem Cell Researchen
dc.subjectStem Cell Research - Nonembryonic - Non-Humanen
dc.subject1 Underpinning researchen
dc.subject1.1 Normal biological development and functioningen
dc.subjectCardiovascularen
dc.subject3201 Cardiovascular medicine and haematologyen
dc.subject3202 Clinical sciencesen
dc.subject.meshPericytesen
dc.subject.meshEndothelial Cellsen
dc.subject.meshAnimalsen
dc.subject.meshMiceen
dc.subject.meshConnexinsen
dc.subject.meshConnexin 43en
dc.subject.meshCell Differentiationen
dc.titlePericyte Progenitor Coupling to the Emerging Endothelium during Vasculogenesis via Connexin43en
dc.title.serialArteriosclerosis, Thrombosis, and Vascular Biologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dcterms.dateAccepted2022-01-24en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicineen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/VTC School of Medicine - Instr Pgmsen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Basic Scienceen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Basic Science/Basic Scienceen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/VTC School of Medicine - Instr Pgms/VTC School of Medicine-Instr Pgmsen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Basic Science/Basic Science/Secondary Appointment-Basic Scienceen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Basic Science/Secondary Appointment-Basic Scienceen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Biomedical Research Institute at VTCen

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