Pericyte heterogeneity identified by 3D ultrastructural analysis of the microvessel wall

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dc.contributor.authorAbdelazim, Hanaaen
dc.contributor.authorPayne, Laura Bethen
dc.contributor.authorNolan, Kyleen
dc.contributor.authorParalkar, Karanen
dc.contributor.authorBradley, Vanessaen
dc.contributor.authorKanodia, Ronaken
dc.contributor.authorGude, Rosalieen
dc.contributor.authorWard, Rachaelen
dc.contributor.authorMonavarfeshani, Aboozaren
dc.contributor.authorFox, Michael A.en
dc.contributor.authorChappell, John C.en
dc.date.accessioned2023-01-31T17:41:03Zen
dc.date.available2023-01-31T17:41:03Zen
dc.date.issued2022-12-16en
dc.date.updated2023-01-31T03:11:59Zen
dc.description.abstractConfident identification of pericytes (PCs) remains an obstacle in the field, as a single molecular marker for these unique perivascular cells remains elusive. Adding to this challenge is the recent appreciation that PC populations may be heterogeneous, displaying a range of morphologies within capillary networks. We found additional support on the ultrastructural level for the classification of these PC subtypes—“thin-strand” (TSP), mesh (MP), and ensheathing (EP)—based on distinct morphological characteristics. Interestingly, we also found several examples of another cell type, likely a vascular smooth muscle cell, in a medial layer between endothelial cells (ECs) and pericytes (PCs) harboring characteristics of the ensheathing type. A conserved feature across the different PC subtypes was the presence of extracellular matrix (ECM) surrounding the vascular unit and distributed in between neighboring cells. The thickness of this vascular basement membrane was remarkably consistent depending on its location, but never strayed beyond a range of 150–300 nm unless thinned to facilitate closer proximity of neighboring cells (suggesting direct contact). The density of PC-EC contact points (“peg-and-socket” structures) was another distinguishing feature across the different PC subtypes, as were the apparent contact locations between vascular cells and brain parenchymal cells. In addition to this thinning, the extracellular matrix (ECM) surrounding EPs displayed another unique configuration in the form of extensions that emitted out radially into the surrounding parenchyma. Knowledge of the origin and function of these structures is still emerging, but their appearance suggests the potential for being mechanical elements and/or perhaps signaling nodes via embedded molecular cues. Overall, this unique ultrastructural perspective provides new insights into PC heterogeneity and the presence of medial cells within the microvessel wall, the consideration of extracellular matrix (ECM) coverage as another PC identification criteria, and unique extracellular matrix (ECM) configurations (i.e., radial extensions) that may reveal additional aspects of PC heterogeneity.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3389/fphys.2022.1016382en
dc.identifier.eissn1664-042Xen
dc.identifier.issn1664-042Xen
dc.identifier.orcidChappell, John [0000-0002-0427-5170]en
dc.identifier.orcidFox, Michael [0000-0002-1649-7782]en
dc.identifier.otherPMC9800988en
dc.identifier.other1016382 (PII)en
dc.identifier.pmid36589416en
dc.identifier.urihttp://hdl.handle.net/10919/113587en
dc.identifier.volume13en
dc.language.isoenen
dc.publisherFrontiersen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/36589416en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectcerebrovasculatureen
dc.subjectendothelial cellsen
dc.subjectextracellular matrixen
dc.subjectpericyteen
dc.subjectsmooth muscle cellsen
dc.subjectultrastructureen
dc.titlePericyte heterogeneity identified by 3D ultrastructural analysis of the microvessel wallen
dc.title.serialFrontiers in Physiologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherJournal Articleen
dcterms.dateAccepted2022-12-05en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Science/COS T&R Facultyen
pubs.organisational-group/Virginia Tech/Science/School of Neuroscienceen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicineen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Basic Scienceen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Pediatricsen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Basic Science/Basic Scienceen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Pediatrics/General Pediatricsen
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/Pediatrics/General Pediatrics/Secondary Appointment-Pediatricsen
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
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Pediatrics/Secondary Appointments-Pediatricsen

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