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

Zhen Miao, Michael S. Balzer, Ziyuan Ma, Hongbo Liu, Junnan Wu, Rojesh Shrestha, Tamas Aranyi, Amy Kwan, Ayano Kondo, Marco Pontoglio, Junhyong Kim, Mingyao Li, Klaus H. Kaestner and Katalin Susztak ()
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Zhen Miao: Perelman School of Medicine
Michael S. Balzer: Perelman School of Medicine
Ziyuan Ma: Perelman School of Medicine
Hongbo Liu: Perelman School of Medicine
Junnan Wu: Perelman School of Medicine
Rojesh Shrestha: Perelman School of Medicine
Tamas Aranyi: Perelman School of Medicine
Amy Kwan: Perelman School of Medicine
Ayano Kondo: Perelman School of Medicine
Marco Pontoglio: Institut Necker Enfants Malades
Junhyong Kim: University of Pennsylvania
Mingyao Li: Perelman School of Medicine
Klaus H. Kaestner: Perelman School of Medicine
Katalin Susztak: Perelman School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: Abstract 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22266-1

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DOI: 10.1038/s41467-021-22266-1

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