Dynamics of cell states and alternative splicing following kidney ischemia-reperfusion injury
Markiewitz, D.; Goldberger, J.; Kalisky, T.
Show abstract
The progression of kidney damage in chronic kidney disease (CKD) involves multiple post-injury stages and complex cellular and molecular mechanisms that are not yet fully understood. In our study we set to characterize the dynamics of mRNA splicing following kidney injury. To this end, we analyzed publicly available bulk RNA-seq data covering nine time points following a kidney ischemia-reperfusion injury (IRI) mouse experiment. Using topic modeling we discerned five distinct temporal phases corresponding to the following cell states: "early injury response", "injury", "repairing", "failed recovery", and "healthy proximal tubule". Additionally, we discovered a set of genes that are alternatively spliced between selected time points associated with these cell states, some of which are related to injury, stress, EMT, and apoptosis. Finally, we found several putative splicing regulators that are differentially expressed between the different time points and whose binding motifs are enriched in the vicinity of alternatively spliced exons, indicating that they may play critical roles in mRNA splicing dynamics following kidney injury and repair. These findings enhance our understanding of the molecular mechanisms involved in kidney injury and repair, offering potential avenues for developing targeted therapeutic strategies for acute kidney injury (AKI) and its progression to CKD.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Renal Interstitial Cells Promote Nephron Regeneration by Secreting Prostaglandin E2 95%
- A β-catenin-driven switch in TCF/LEF transcription factor binding to DNA target sites promotes commitment of mammalian nephron progenitor cells 94%
- Empagliflozin reduces renal lipotoxicity in experimental Alport syndrome 92%
Similar papers in this journal
- Single Cell Profiling of Acute Kidney Injury Reveals Novel Transcriptional Signatures, Mixed Identities and Epithelial-to-Stromal Crosstalk 95%
- Single-cell RNA sequencing reveals mRNA splice isoform switching during kidney development 94%
- Tripartite separation of glomerular cell-types and proteomes from reporter-free mice 93%
Similar papers in this journal
- RESIC: A tool for comprehensive adenosine to inosine RNA Editing Site Identification and Classification 92%
- Genetic Association and Transferability for Urinary Albumin-Creatinine Ratio as a Marker of Kidney Disease in four Sub-Saharan African Populations and non-continental Individuals of African Ancestry 91%
- A comprehensive prediction of transcript isoforms in 19 chicken tissues by Oxford Nanopore long-read sequencing 91%
Similar papers in this journal
- Long read subcellular fractionation and sequencing reveals the translational fate of full length mRNA isoforms during neuronal differentiation 92%
- Accurately estimating pathway activity in single cells for clustering and differential analysis 92%
- Tracking pre-mRNA maturation across subcellular compartments identifies developmental gene regulation through intron retention and nuclear anchoring. 91%
Similar papers in this journal
- Long read sequencing reveals novel isoforms and insights into splicing regulation during cell state changes 91%
- Revealing the Prevalence of Suboptimal Cells and Organs in Reference Cell Atlases: An Imperative for Enhanced Quality Control 90%
- Cataloging the potential functional diversity of Cacna1e splice variants using long-read sequencing 90%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.