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Identification and lineage analysis of Hic1⁺ and Pdgfra⁺ presumptive mesenchymal progenitors in the adult murine kidney Samani, Atefeh M. V.

Abstract

The increase in kidney disease incidence and its associated comorbidities has become a global issue. Repeated bouts of acute insults or chronic injury can significantly compromise normal phsyiological functions of the kidney such as glomerular filtration. If left untreated, these issues may progress to end stage renal disease (ESRD) which oftentimes culminates in death. Because the kidney is composed of several hundred thousand functional units called nephrons, it is highly likely that normal physiological wear and tear does not significantly impact kidney function such that it would activate a reparative or regenerative process. However there is evidence which suggests that the kidney may resume normal function following isolated yet severe instances of acute kidney injury. This may involve the activity of kidney-resident mesenchymal progenitors (MPs). Thus far, renal progenitor populations and their coordinated interactions remain largely undefined. Previously, our lab has identified and characterized Hic1 as a possible marker of MPs that can regulate tissue regenerative processes in various tissues. Pdgfra has also been identified as a marker of MPs with similar capacities. Given this information, we were interested in examining the spacial localization of both these markers and comparing their incidence in young and mature adult murine kidney. Using a variety of mouse genetic models and fluorescence microscopy we found that Hic1⁺, Pdgfra⁺, as well as , Hic1⁺Pdgfra⁺ populations, were localized in the mesangial compartment and juxtaglomerular apparatus (JA) of glomeruli. Our quantitative analysis also revealed that there are significantly more Pdgfra⁺ MPs in mature adult mice when compared to young adult mice. We were interested in further parsing out the heterogeneity in the Hic1⁺ compartment. Bioinformatic analysis revealed 5 unique clusters from which we identified highly enriched and unique markers. Markers indicative of some of these different populations such as GATA3 and ADORA1 were used to identify these poptulations in situ. Both of these markers labelled cells within the mesangial compartments and JA. The results from this study yield important insights into the nature of tissue-resident MPs in the kidney, thereby providing a foundation to support their study in kidney renewal and regeneration.

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