BioProject

Purpose: Loss of DIS3L2 in humans is associated with congenital overgrowth in Perlman syndrome, as well as with the development of Wilms tumors. More...

Purpose: Loss of DIS3L2 in humans is associated with congenital overgrowth in Perlman syndrome, as well as with the development of Wilms tumors. DIS3L2 is an exoribonuclease with a demonstrated preference for 3’-uridylated RNA substrates. However, its targets relevant to human disease are poorly understood. Our goal was to address transcriptomic changes in DIS3L2 deficient mouse nephron progenitor cells, a cell type of the developing kidney with demonstrated relevance to Wilms tumorigenesis. Methods: RNA-seq libraries were prepared using the TruSeq Stranded Total RNA LT Sample Prep Kit (Illumina) and sequenced using 50 base pair single-end reads on an Illumia HiSeq2500 at the McDermott Center Next Generation Sequencing core at UT Southwestern. Samples were 2 biological replicates of wild-type and 3 of Dis3l2-null from embryos of the same litter. Results: Upregulated genes included replication-dependent histone mRNA and small non-coding Polymerase III transcripts, as expected from previous reports, as well as Igf2, a gene that has not previously been established to be regulated by DIS3L2 and whose upregulation is associated with overgrowth and Wilms tumor development. Conclusions: These data implicate Igf2 as a promising candidate for the overgrowth and Wilms tumorigenesis observed in DIS3L2-deficient disease states. Overall design: Gene expression profiles of Dis3l2 null or wild-type primary nephron progenitor cells were determined by RNA-seq. Less...