Hong Kong University of Science and Technology, Hong Kong
Abstract: Stem cell exhaustion is one of the hallmarks of biological aging. It has been shown that stem cell exhaustion is heterogeneous among aged organs and tissues. The kidney is one of the most vulnerable organs to aging, and aging plays a leading role in various renal diseases. However, the existence of stem cells in adult primate kidney and their alterations during aging remain unclear. Here, we made use of single-nuclei RNA sequencing (snRNA-seq) to uncover the stem cells in the adult kidney of the cynomolgus monkey (Macaca fascicularis). Notably, a subpopulation of principle cells, namely stem-like cells, was found in the root of pseudotime trajectory with distinctive expression of known stem cell markers, including prominin-1 (Prom1), compared to the other cell populations. In addition, the level of stemness and stemness-related transcription factors of these stem-like cells were significantly higher than the remaining cell populations as estimated using CytoTrace2 and Pyscenic. Further, we compared the stem-like cells from young, middle-aged, and old monkey kidney to characterize their aging-related alterations. Interestingly, the population of stem-like cells in the kidney was expanded during aging, which was thought to be reduced with age. We then examined the expression level of proliferation markers, the differentiation potential, and the stemness levels of these stem-like cells during aging. All of them were declined along with age. It suggested that the aberrant accumulation of stem-like cells in primate kidney is due to stem cell exhaustion characterized by impaired proliferation and differentiation capacity. Collectively, we identified a stem-like cell population in non-human primate kidney and found that exhausted stem-like cells accumulated in the kidney during aging, which could serve as a promising therapeutic target of kidney rejuvenation.
Funding Source: RGC Theme-based Research Scheme (T13-602/21N)
