RT Journal Article
SR Electronic
T1 Characterization of splice isoform switching during human kidney development
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 816371
DO 10.1101/816371
A1 Yishay Wineberg
A1 Itamar Kanter
A1 Nissim Ben-Haim
A1 Naomi Pode-Shakked
A1 Efrat Bucris
A1 Tali Hana Bar-Lev
A1 Sarit Oriel
A1 Yishai Yehuda
A1 Rotem Gershon
A1 Rachel Shukrun
A1 Dekel Dov Bar-Lev
A1 Achia Urbach
A1 Benjamin Dekel
A1 Tomer Kalisky
YR 2019
UL http://biorxiv.org/content/early/2019/10/24/816371.abstract
AB Nephrons are the functional units of the kidney. During kidney development, cells from the cap mesenchyme – a transient kidney-specific progenitor state – undergo a mesenchymal to epithelial transition (MET) and subsequently differentiate into the various epithelial cell types that create the tubular structures of the nephron. Faults in this transition can lead to a pediatric malignancy of the kidney called Wilms’ tumor that mimics normal kidney development. While kidney development has been characterized at the gene expression level, a comprehensive characterization of alternative splicing is lacking. We therefore performed RNA sequencing on cell populations representing early, intermediate, and late developmental stages of the human fetal kidney, as well as three blastemal-predominant Wilms’ tumor patient-derived xenografts. We identified a set of transcripts that are alternatively spliced between the different developmental stages. Moreover, we found that cells from the earliest developmental stage have a mesenchymal splice-isoform profile that is similar to that of blastemal-predominant Wilms’ tumors. RNA binding motif enrichment analysis suggests that the mRNA binding proteins ESRP1, ESRP2, RBFOX2, and QKI regulate mRNA splice isoform switching during human kidney development. These findings illuminate new molecular mechanisms involved in kidney development and pediatric kidney tumors.HIGHLIGHTSDuring fetal kidney development, kidney progenitor cells undergo a mesenchymal to epithelial transition (MET) and subsequently differentiate into the various epithelial cell types that create the tubular structures of the nephron.RNA sequencing identifies a set of transcripts that undergo splice isoform switching during the mesenchymal to epithelial transition (MET) that occurs in the course of human fetal kidney development.Cells in the early stages of kidney development have a mesenchymal splice-isoform profile that is similar to that observed in blastemal-predominant Wilms’ tumor patient-derived xenografts (WT-PDX) that represent an aggressive subtype of Wilms’ tumors.RNA binding motif enrichment analysis indicates that the mRNA binding proteins ESRP1, ESRP2, RBFOX2, and QKI regulate splice isoform switching during human kidney development.