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Unraveling Epigenetic and Immune Mechanisms Underlying Cystogenesis in Autosomal Dominant Polycystic Kidney Disease [ATAC-Seq]

GSE244997 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 4 samples Submitted 2024/10/10 Platform GPL24247
Summary
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a prevalent, life-threatening monogenetic disorder that affects millions worldwide. Currently, therapeutic options are limited and often associated with complications. To find more effective treatments, this study aimed to understand the molecular mechanisms driving cystogenesis in ADPKD. By analysing various epigenetic factors, we identified a set of master transcription factors that guided a core regulatory circuitry and remodeled chromatin accessibility in ADPKD. We further explored the role of immune cells, notably macrophages, in the disease’s progression using single-cell RNA sequencing. A subgroup of Lhfpl2+/Fat3+ macrophages, which reactivated the Hgf-Met-Nfkb1-Runx1 pathways, was found essential for cystic cell fate transition. Targeting the identified epigenetic regulators, H3K4me3 and TF Runx1, effectively halted disease progression in a mouse model. These findings may lead to innovative treatments for ADPKD in humans.
Published in
Epigenomic, cistromic, and transcriptomic profiling of primary kidney tubular cells
Liu Z, Zhang L, Chen Y · Journal of biological methods 2024 · PMID 39323486 · doi:10.14440/jbm.2024.0009
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Direct links to NCBI, no account and no request form: the whole study as GSE244997_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 4 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1026592 and SRA study SRP465487. Searching any of these in the dataset finder brings you back here.

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