Single cell regulatory landscape of the mouse kidney highlights cellular differentiation programs and disease targets.

Autor: Miao Z; Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.; Graduate Group in Genomics and Computational Biology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA., Balzer MS; Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA., Ma Z; Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA., Liu H; Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA., Wu J; Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA., Shrestha R; Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA., Aranyi T; Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA., Kwan A; Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA., Kondo A; Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA., Pontoglio M; Epigenetics and Development Laboratory, Université de Paris Inserm U1151/CNRS UMR 8253, Institut Necker Enfants Malades, Paris, France., Kim J; Department of Biology, University of Pennsylvania, Philadelphia, PA, USA., Li M; Department of Epidemiology and Biostatistics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA., Kaestner KH; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.; Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA., Susztak K; Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA. ksusztak@pennmedicine.upenn.edu.; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA. ksusztak@pennmedicine.upenn.edu.; Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA. ksusztak@pennmedicine.upenn.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Apr 15; Vol. 12 (1), pp. 2277. Date of Electronic Publication: 2021 Apr 15.
DOI: 10.1038/s41467-021-22266-1
Abstrakt: Determining the epigenetic program that generates unique cell types in the kidney is critical for understanding cell-type heterogeneity during tissue homeostasis and injury response. Here, we profile open chromatin and gene expression in developing and adult mouse kidneys at single cell resolution. We show critical reliance of gene expression on distal regulatory elements (enhancers). We reveal key cell type-specific transcription factors and major gene-regulatory circuits for kidney cells. Dynamic chromatin and expression changes during nephron progenitor differentiation demonstrates that podocyte commitment occurs early and is associated with sustained Foxl1 expression. Renal tubule cells follow a more complex differentiation, where Hfn4a is associated with proximal and Tfap2b with distal fate. Mapping single nucleotide variants associated with human kidney disease implicates critical cell types, developmental stages, genes, and regulatory mechanisms. The single cell multi-omics atlas reveals key chromatin remodeling events and gene expression dynamics associated with kidney development.
Databáze: MEDLINE
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