Chromatin accessibility and microRNA expression in nephron progenitor cells during kidney development

• Published in: Genomics (San Diego, Calif.) Vol. 114; no. 1; pp. 278 - 291
• Main Authors: Clugston, Andrew, Bodnar, Andrew, Cerqueira, Débora Malta, Phua, Yu Leng, Lawler, Alyssa, Boggs, Kristy, Pfenning, Andreas R., Ho, Jacqueline, Kostka, Dennis
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2022
• Subjects: Animals; Cell Differentiation - genetics; Chromatin - genetics; Chromatin - metabolism; Chromatin accessibility; Gene regulation; Gene-regulatory elements; Kidney - metabolism; Kidney development; Mammals - genetics; Mice; microRNA; MicroRNAs - genetics; MicroRNAs - metabolism; Nephron progenitor cells; Nephrons - metabolism; Stem Cells; Nephron progenitor cells; microRNA; Gene-regulatory elements; Chromatin accessibility; Gene regulation; Kidney development
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1016/j.ygeno.2021.12.017

Mammalian nephrons originate from a population of nephron progenitor cells, and changes in these cells' transcriptomes contribute to the cessation of nephrogenesis, an important determinant of nephron number. To characterize microRNA (miRNA) expression and identify putative cis-regulatory regions, we collected nephron progenitor cells from mouse kidneys at embryonic day 14.5 and postnatal day zero and assayed small RNA expression and transposase-accessible chromatin. We detect expression of 1104 miRNA (114 with expression changes), and 46,374 chromatin accessible regions (2103 with changes in accessibility). Genome-wide, our data highlight processes like cellular differentiation, cell migration, extracellular matrix interactions, and developmental signaling pathways. Furthermore, they identify new candidate cis-regulatory elements for Eya1 and Pax8, both genes with a role in nephron progenitor cell differentiation. Finally, we associate expression-changing miRNAs, including let-7-5p, miR-125b-5p, miR-181a-2-3p, and miR-9-3p, with candidate cis-regulatory elements and target genes. These analyses highlight new putative cis-regulatory loci for miRNA in nephron progenitors. •Nephron progenitor cells express distinct microRNAs in embryonic development (day 14.5) compared with postnatal day 0.•Chromatin accessibility also differs between nephron progenitor cells at these points.•Using information about topologically associated domains helps identify putative enhancer – micro-RNA interactions.