The chromatin landscape of healthy and injured cell types in the human kidney
Human kidney
DOI:
10.1038/s41467-023-44467-6
Publication Date:
2024-02-01T12:02:51Z
AUTHORS (353)
ABSTRACT
There is a need to define regions of gene activation or repression that control human kidney cells in states health, injury, and repair understand the molecular pathogenesis disease design therapeutic strategies. Comprehensive integration expression with epigenetic features regulatory elements remains significant challenge. We measure dual single nucleus RNA chromatin accessibility, DNA methylation, H3K27ac, H3K4me1, H3K4me3, H3K27me3 histone modifications decipher landscape regulation reference adaptive injury states. establish spatially-anchored epigenomic atlas kidney's active, silent, accessible across genome. Using this atlas, we note distinct different epithelial cell types. A proximal tubule transcription factor network ELF3, KLF6, KLF10 regulates transition between health while thick ascending limb regulated by NR2F1. Further, combined perturbation distinguishes two tubular subtypes, one which manifested trajectory after knockout. This will serve as foundation facilitate targeted cell-specific therapeutics reprogramming networks.
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