Distinct fibroblast progenitor subpopulation expedites regenerative mucosal healing by immunomodulation

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dc.contributor.authorKo, Kang I.
dc.contributor.authorDergarabedian, Brett P.
dc.contributor.authorChen, Zhaoxu
dc.contributor.authorDebnath, Rahul
dc.contributor.authorKo, Annette
dc.contributor.authorLink, Brittany N.
dc.contributor.authorKorostoff, Jonathan M.
dc.contributor.authorGraves, Dana T.
dc.date.accessioned2025-01-16T16:12:13Z
dc.date.available2025-01-16T16:12:13Z
dc.date.copyright2023-03-06
dc.date.issued2023-06-03
dc.description.abstractInjuries that heal by fibrosis can compromise organ function and increase patient morbidity. The oral mucosal barrier has a high regenerative capacity with minimal scarring, but the cellular mechanisms remain elusive. Here, we identify distinct postnatal paired-related homeobox-1+ (Prx1+) cells as a critical fibroblast subpopulation that expedites mucosal healing by facilitating early immune response. Using transplantation and genetic ablation model in mice, we show that oral mucosa enriched with Prx1+ cells heals faster than those that lack Prx1+ cells. Lineage tracing and scRNA-seq reveal that Prx1+ fibroblasts exhibit progenitor signatures in physiologic and injured conditions. Mechanistically, Prx1+ progenitors accelerate wound healing by differentiating into immunomodulatory SCA1+ fibroblasts, which prime macrophage recruitment through CCL2 as a key part of pro-wound healing response. Furthermore, human Prx1+ fibroblasts share similar gene and spatial profiles compared to their murine counterpart. Thus, our data suggest that Prx1+ fibroblasts may provide a valuable source in regenerative procedures for the treatment of corneal wounds and enteropathic fibrosis. © 2022 Ko et al.
dc.identifier.urihttps://repository.upenn.edu/handle/20.500.14332/60800
dc.publisherRockefeller University Press
dc.relation.doi10.1084/jem.20221350
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.source.issue3
dc.source.journaltitleJournal of Experimental Medicine
dc.source.volume220
dc.subjectDentistry
dc.subject.otherCicatrix
dc.subject.otherFibrosis
dc.subject.otherImmunomodulation
dc.titleDistinct fibroblast progenitor subpopulation expedites regenerative mucosal healing by immunomodulation
dc.typeArticle
dspace.entity.typePublication
upenn.schoolDepartmentCenterSchool of Dental Medicine::Departmental Papers (Dental)
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