RT Journal Article
SR Electronic
T1 Single cell resolution regulatory landscape of the mouse kidney highlights cellular differentiation programs and renal disease targets
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.24.113910
DO 10.1101/2020.05.24.113910
A1 Zhen Miao
A1 Michael S. Balzer
A1 Ziyuan Ma
A1 Hongbo Liu
A1 Junnan Wu
A1 Rojesh Shrestha
A1 Tamas Aranyi
A1 Amy Kwan
A1 Ayano Kondo
A1 Marco Pontoglio
A1 Junhyong Kim
A1 Mingyao Li
A1 Klaus H. Kaestner
A1 Katalin Susztak
YR 2020
UL http://biorxiv.org/content/early/2020/06/04/2020.05.24.113910.abstract
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.