PT  - JOURNAL ARTICLE
AU  - Zhen Miao
AU  - Michael S. Balzer
AU  - Ziyuan Ma
AU  - Hongbo Liu
AU  - Junnan Wu
AU  - Rojesh Shrestha
AU  - Tamas Aranyi
AU  - Amy Kwan
AU  - Ayano Kondo
AU  - Marco Pontoglio
AU  - Junhyong Kim
AU  - Mingyao Li
AU  - Klaus H. Kaestner
AU  - Katalin Susztak
TI  - Single cell resolution regulatory landscape of the mouse kidney highlights cellular differentiation programs and renal disease targets
AID  - 10.1101/2020.05.24.113910
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.05.24.113910
4099  - http://biorxiv.org/content/early/2020/06/04/2020.05.24.113910.short
4100  - http://biorxiv.org/content/early/2020/06/04/2020.05.24.113910.full
AB  - 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 profiled 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 define key cell type-specific transcription factors and major gene-regulatory circuits for kidney cells. Dynamic chromatin and expression changes during nephron progenitor differentiation demonstrated that podocyte commitment occurs early and is associated with sustained Foxl1 expression. Renal tubule cells followed a more complex differentiation, where Hfn4a was associated with proximal and Tfap2b with distal fate. Mapping single nucleotide variants associated with human kidney disease identified critical cell types, developmental stages, genes, and regulatory mechanisms.We provide a global single cell resolution view of chromatin accessibility of kidney development. The dataset is available via interactive public websites.Competing Interest StatementThe authors have declared no competing interest.