The landscape of allele-specific expression in human kidneys
Year: 2026
Type: article
Study design: Observational Study
Abstract: Allele-specific expression (ASE), the preferential expression of one gene copy, is a key mechanism of genomic regulation. However, its role in human kidney disease remains poorly understood. In this study, we generated a high-quality, genome-wide ASE map using paired whole-genome sequencing and RNA-seq from microdissected glomerular (GLOM) and tubulointerstitial (TUBE) compartments of patients with proteinuric kidney disease. We showed that the majority of common ASE events were deterministic and sequence-mediated. We also found that diseased kidneys exhibited significantly more ASE in GLOM than TUBE, compared to controls. Unexpectedly, higher ASE in GLOM than TUBE was significantly associated with improved kidney disease outcomes in the disease cohort. Differential gene expression analysis suggested this was the result of an active, protective transcriptional response, including ribosome and ATP synthesis upregulation, rather than pathogenic dysregulation. Our work reveals glomerular ASE as a marker of adaptive transcriptional activity in proteinuric kidney disease.
Source: Science Advances
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
Awards: Harvard Chronic Kidney Disease Research Biopsy Center, Mutations in TBC1D8B as a potential new cause of nephrotic syndrome, Multidimensional cellular interrogation of the kidney in AKI and CKD, Phenotyping REnal Cases In Sepsis and surgery for Early Acute Kidney Injury (PReCISE AKI), Deep learning and topological approaches to identify kidney tissue features associated with adverse outcomes after nephrectomy, Kidney Precision Medicine Program (KPMP): Columbia AKI Recruitment Site, Nephrotic Syndrome Rare Disease Clinical Research Network III, G9000849256, G9000849377, Spatial Elucidation of Human Acute Kidney Injury and Chronic Kidney Disease using Imaging Mass Cytometry, PREcision Medicine through IntErrogation of Rna in the kidnEy (PREMIERE), Minnesota Precision Medicine CKD & Resilient Diabetes Recruiting Site: Engagement, Enrollment & Ethics, Integrated spatial interrogation of cellular and molecular signatures of human kidney disease, Single cell multiomic and spatial atlas of acute and chronic kidney injury, Mount Sinai Health System Kidney Precision Medicine Project, University of Illinois at Chicago KPMP CKD Recruitment Site, AKI Matched Phenotype Linked Evaluation with Tissue (AMPLE-Tissue), Central Hub for Kidney Precision Medicine, Data Management and Coordinating Center: Rare Diseases Clinical Research Network, Multimodal Imaging Mass Spectrometry and Spatial Omics for the Human Kidney, Boston Chronic Kidney Disease Research Biopsy Center, Cleveland Precision Medicine Chronic Kidney Disease Cohort, Kidney Precision Medicine Project - Patient Engagement, KPMP Kidney Mapping and Atlas Project (KMAP), Geographic and Environmental Health Equity in Kidney Precision Medicine, Spatial Multi-Omics to Profile Metabolic Pathways for Kidney Disease, Spatial Mapping of Proteomic and Transcriptional Signatures in Kidney Disease
OpenAlex ID: W7215779622