Single cell transcriptional and chromatin accessibility profiling redefine cellular heterogeneity in the adult human kidney
Yoshiharu Muto,
Parker C. Wilson,
Nicolas Ledru,
Haojia Wu,
Henrik Dimke,
Sushrut S. Waikar and
Benjamin D. Humphreys ()
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Yoshiharu Muto: Washington University in St. Louis
Parker C. Wilson: Washington University in St. Louis
Nicolas Ledru: Washington University in St. Louis
Haojia Wu: Washington University in St. Louis
Henrik Dimke: Institute of Molecular Medicine, University of Southern Denmark
Sushrut S. Waikar: Boston University School of Medicine and Boston Medical Center
Benjamin D. Humphreys: Washington University in St. Louis
Nature Communications, 2021, vol. 12, issue 1, 1-17
Abstract:
Abstract The integration of single cell transcriptome and chromatin accessibility datasets enables a deeper understanding of cell heterogeneity. We performed single nucleus ATAC (snATAC-seq) and RNA (snRNA-seq) sequencing to generate paired, cell-type-specific chromatin accessibility and transcriptional profiles of the adult human kidney. We demonstrate that snATAC-seq is comparable to snRNA-seq in the assignment of cell identity and can further refine our understanding of functional heterogeneity in the nephron. The majority of differentially accessible chromatin regions are localized to promoters and a significant proportion are closely associated with differentially expressed genes. Cell-type-specific enrichment of transcription factor binding motifs implicates the activation of NF-κB that promotes VCAM1 expression and drives transition between a subpopulation of proximal tubule epithelial cells. Our multi-omics approach improves the ability to detect unique cell states within the kidney and redefines cellular heterogeneity in the proximal tubule and thick ascending limb.
Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22368-w
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DOI: 10.1038/s41467-021-22368-w
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