RT Journal Article
SR Electronic
T1 Defining the dynamic chromatin landscape of nephron progenitors
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 515429
DO 10.1101/515429
A1 Sylvia Hilliard
A1 Renfang Song
A1 Hongbing Liu
A1 Chao-hui Chen
A1 Yuwen Li
A1 Melody Baddoo
A1 Erik Flemington
A1 Alanna Wanek
A1 Jay Kolls
A1 Zubaida Saifudeen
A1 Samir S. El-Dahr
YR 2019
UL http://biorxiv.org/content/early/2019/01/08/515429.abstract
AB Six2+ cap mesenchyme cells, also called nephrons progenitor cells (NPC), are precursors of all epithelial cell types of the nephron, the filtering unit of the kidney. Current evidence indicates that perinatal “old” NPC have a greater tendency to exit the progenitor niche and differentiate into nascent nephrons than their embryonic “young” counterpart. Understanding the underpinnings of NPC aging may offer insights to rejuvenate old NPC and expand the progenitor pool. Here, we compared the chromatin landscape of young and old NPC and found common features reflecting their shared lineage but also intrinsic differences in chromatin accessibility and enhancer landscape supporting the view that old NPC are epigenetically poised for differentiation. Annotation of open chromatin regions and active enhancers uncovered the transcription factor Bach2 as a potential link between the pro-renewal MAPK/AP1 and pro-differentiation Six2/b-catenin pathways that might be of critical importance in regulation of NPC fate. Our data provide the first glimpse of the dynamic chromatin landscape of NPC and serve as a platform for future studies of the impact of genetic or environmental perturbations on the epigenome of NPC.Summary statement Hilliard et al. investigated the chromatin landscape of native Six2+ nephron progenitors across their lifespan. They identified age-dependent changes in accessible chromatin and regulatory regions supporting the view that old nephron progenitors are epigenetically poised for differentiation.