Defining the dynamic chromatin landscape of mouse nephron progenitors
Sylvia Hilliard,
Renfang Song,
Hongbing Liu,
Chao-hui Chen,
Yuwen Li,
Melody Baddoo,
Erik Flemington,
Alanna Wanek,
Jay Kolls,
Zubaida Saifudeen,
Samir S. El-Dahr
Affiliations
Sylvia Hilliard
Department of Pediatrics, Section of Pediatric Nephrology, Tulane University School of Medicine, New Orleans, LA 70112, USA
Renfang Song
Department of Pediatrics, Section of Pediatric Nephrology, Tulane University School of Medicine, New Orleans, LA 70112, USA
Hongbing Liu
Department of Pediatrics, Section of Pediatric Nephrology, Tulane University School of Medicine, New Orleans, LA 70112, USA
Chao-hui Chen
Department of Pediatrics, Section of Pediatric Nephrology, Tulane University School of Medicine, New Orleans, LA 70112, USA
Yuwen Li
Department of Pediatrics, Section of Pediatric Nephrology, Tulane University School of Medicine, New Orleans, LA 70112, USA
Melody Baddoo
Department of Pathology & Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112, USA
Erik Flemington
Department of Pathology & Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112, USA
Alanna Wanek
Departments of Pediatrics & Medicine, Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, LA 70112, USA
Jay Kolls
Departments of Pediatrics & Medicine, Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, LA 70112, USA
Zubaida Saifudeen
Department of Pediatrics, Section of Pediatric Nephrology, Tulane University School of Medicine, New Orleans, LA 70112, USA
Samir S. El-Dahr
Department of Pediatrics, Section of Pediatric Nephrology, Tulane University School of Medicine, New Orleans, LA 70112, USA
Six2+ cap mesenchyme cells, also called nephron 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 development 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.
