Multimodal single cell sequencing implicates chromatin accessibility and genetic background in diabetic kidney disease progression. Multimodal single cell sequencing implicates chromatin accessibility and genetic background in diabetic kidney disease progression

Purpose: Single cell sequencing has advanced our understanding of kidney biology. The goals of this study are to compare single nucleus RNA (snRNA-seq) and single nucleus assay for transposase accessible chromatin sequencing (snATAC-seq) from healthy control donors and donors with type 2 diabetic kidney disease to identify altered signaling pathways and chromatin accessibility patterns observed in diabetic kidney disease. Methods: Nuclear dissociation of human kidney cortex samples was performed on samples obtained from patients undergoing tumor nephrectromy or deceased organ donors. snRNA-seq and snATAC-seq libraries were prepared using 10X Genomics kits according to manufacturers instructions. For this study, two healthy control libraries from one donor were prepared with the following chemistries (1 - single cell 3-prime v3, 1 - single cell ATAC v1) and nine DKD libraries from seven donors were prepared with the following chemistries (2 - single cell 5-prime v2 paired-end, 7 - single cell ATAC v1). Raw data for three healthy control and three DKD snRNA-seq libraries sequenced with single nucleus 5-prime R2 only can be found in GSE13188213. Raw data for two healthy control snRNA-seq sequenced with single nucleus 5-prime paired-end and five snATAC-seq single nucleus ATAC v1 libraries can be found in GSE151302. snRNA-seq and snATAC-seq libraries from these earlier studies were recounted with cellranger (v4.0) or cellranger-atac (v2.0) to provide consistency across processed data files. Overall design: snRNA-seq and snATAC-seq of human kidney cortex from patients with and without type 2 diabetic kidney disease