Global transcriptomic changes occur in aged mouse podocytes

The Intertwining of Autophagy and the Ubiquitin Proteasome System in Podocyte (Patho)Physiology

“…Accumulation of damaged organelles such as mitochondria as well as protein aggregates is the common theme of ageing cells, a process from which podocytes are not exempt. Recent comparative measurements of the transcriptomic signature of young and aged murine podocytes exhibit differential regulation of cellular pathways, which affect or are involved in the regulation of autophagy and the proteasome, such as the PI3K-mTOR pathway and the p53 pathway [146]. As a main theme, however, this study revealed an increase of apoptosis and senescence related transcripts in aged podocytes [146].…”

The transcriptomic signature of the aging podocyte

“…Single-cell analysis could be a powerful tool to resolve such changes. Despite these weaknesses, publicly available datasets from aging kidneys showed good correlation with the results reported by Wang et al 6 The next steps should include functional validation of the identified pathways, which will necessitate the generation of novel genetically modified animal models and correlate changes in gene expression and phenotype development such as albuminuria and glomerular filtration rate. Correlation between mouse models and human samples will be important to understand the relevance of changes observed in mice for our patient samples.…”

“…In this issue, Wang et al 6 investigated global transcriptome changes in young (8-to 12-week-old) and aged (88-to 96week-old) podocytes. The team used 2 complementary approaches, including isolating fluorescent-labelled podocytes from the NPHS2Cre-tdTomato mice and magnetic bead-based sorting method.…”

“…The increase in inflammatory phenotype, specifically the increase in the numbers of B and T lymphocytes, was also observed in the Tabula Muris Senis study. 2 Wang et al 6 also performed virtual inference of protein activity by enriched regulon (VIPER) analysis. This analysis provided some very interesting insight into upstream transcription factors that globally regulated gene expression changes.…”

Emerging Single-Cell Technological Approaches to Investigate Chromatin Dynamics and Centromere Regulation in Human Health and Disease

“…Even if the functional relationship between epigenomic and transcriptional dysregulations and neurodegenerative and other age-linked disorders is not clear, the introduction of single-cell sequencing technology has certainly provided more insights about geneexpression differences that originate from specific cell types. Several evidences show that DNA methylation and histone post-translational modifications could play a pivotal function in Alzheimer's disease (AD), in which RNA-seq analysis reveals widespread transcriptomic dysregulation with altered splicing [39]; in ageing-associated phenotype [40], as demonstrated in podocytes of aged mice, in which RNA-seq analysis showed differentially expressed genes to distinct targeting of the ageing process; and in Atherosclerosis, where several genome-wide epigenomic mapping techniques have been performed in a low set of cells [41,42], as also confirmed by the epigenetic alterations in auto-immune disorders [43]. Recently, Mathys et al demonstrated the key role of glial-neuronal interactions in response to AD pathology thanks to a single-cell transcriptomic analysis through which important myelinisation regulators, such as LINGO1, have been identified as alternating between neuronal and glial cells, suggesting their high therapeutic potential [44].…”