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

First Author  Miao Z Year  2021
Journal  Nat Commun Volume  12
Issue  1 Pages  2277
PubMed ID  33859189 Mgi Jnum  J:357085
Mgi Id  MGI:6713706 Doi  10.1038/s41467-021-22266-1
Citation  Miao Z, et al. (2021) Single cell regulatory landscape of the mouse kidney highlights cellular differentiation programs and disease targets. Nat Commun 12(1):2277
abstractText  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.
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