Perivascular fibroblasts in tissue development, maintenance, and repair
Date
2023-10-30
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Abstract
At 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.
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Keywords
Perivascular fibroblasts, Zebrafish, Developmental biology, Fibroblasts
Citation
Rajan, A. (2023). Perivascular fibroblasts in tissue development, maintenance, and repair (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.