Perivascular fibroblasts in tissue development, maintenance, and repair

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dc.contributor.advisorHuang, Peng
dc.contributor.authorRajan, Arsheen
dc.contributor.committeememberChilds, Sarah
dc.contributor.committeememberGrewal, Savraj
dc.contributor.committeememberMcfarlane, Sarah
dc.contributor.committeememberMosimann, Christian
dc.date2024-02
dc.date.accessioned2023-10-31T18:42:43Z
dc.date.available2023-10-31T18:42:43Z
dc.date.issued2023-10-30
dc.description.abstractAt the microscopic scale, all tissues within multicellular organisms are comprised of diverse cell types embedded in a web of extracellular proteins. How each of these components evolve and are maintained as the tissue grows, and how they are replaced upon tissue injury are fundamental questions at the heart of developmental and regenerative biology. One cell type that has emerged in recent years as an essential modulator of tissue growth and repair is the fibroblast. Fibroblasts are multifunctional, tissue-resident mesenchymal cells that are known to regulate the extracellular environment through matrix production and remodeling, coordinate cell differentiation by releasing paracrine signaling factors, and act as multipotent progenitors themselves. Yet, little is known about how different fibroblast subtypes arise and diversify. Therefore, this thesis focuses on exploring the origin, behavior and function of a poorly characterized fibroblast subtype, the perivascular fibroblast, so named due to its localization around blood vessels. In Chapter 1, we summarize current knowledge on blood vessel associated fibroblasts from numerous murine organs. In Chapter 2, we show that in zebrafish, perivascular fibroblasts, arise from the sclerotome region of the somite early in development. We find these perivascular fibroblasts play dual roles in stabilizing the immature vasculature by depositing extracellular structural collagens and giving rise to blood vessel support cells called pericytes. In Chapter 3, I further clarify that perivascular fibroblasts are distinct from other sclerotome-derived fibroblasts in their transcriptional signature, plasticity, and regenerative potential. We show that in response to tendon injury, perivascular fibroblasts actively migrate, proliferate, and differentiate into specialized tendon fibroblasts, tenocytes, to facilitate tissue regeneration. Finally, in Chapter 4, I outline outstanding questions on perivascular fibroblast biology that can be explored in future studies. Together, my work highlights the functional relevance of fibroblast heterogeneity and provides insights into the potential characteristics of homologous perivascular fibroblast-like populations identified in murine and human tissues.
dc.identifier.citationRajan, A. (2023). Perivascular fibroblasts in tissue development, maintenance, and repair (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.urihttps://hdl.handle.net/1880/117488
dc.language.isoen
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgary
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectPerivascular fibroblasts
dc.subjectZebrafish
dc.subjectDevelopmental biology
dc.subjectFibroblasts
dc.subject.classificationBiology--Molecular
dc.subject.classificationBiology--Cell
dc.titlePerivascular fibroblasts in tissue development, maintenance, and repair
dc.typedoctoral thesis
thesis.degree.disciplineMedicine – Biochemistry and Molecular Biology
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.thesis.accesssetbystudentI do not require a thesis withhold – my thesis will have open access and can be viewed and downloaded publicly as soon as possible.
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