Stubbs, Jason R.

Polycystic kidney disease (PKD) arises from mutations in cilia-associated genes, such as PKD1 and PKD2 , expressed in renal epithelial cells, leading to progressive kidney dysfunction and end-stage kidney disease (ESKD). PKD patients exhibit significant heterogeneity in disease progression, largely due to genetic and environmental modifiers. Like patients, mouse models of PKD also exhibit significant heterogeneity with regards to the gene mutated, age of disease onset, and rate of disease progression. To elucidate the cellular and molecular consequences of these variables, we constructed an integrated single-cell RNA sequencing atlas across mouse models of PKD, mapping changes in cell type composition, gene expression, and intercellular signaling networks across the whole atlas and within individual models. Across models, single cell RNA sequencing (scRNAseq) data revealed increased Spp1 (osteopontin) expression and signaling from PKD-enriched clusters. Global deletion of Spp1 in Pkd1 RC/RC mice resulted in a modest reduction in cyst severity and improved kidney function. From these studies, we created a freely available, searchable website (https://bmblx.bmi.osumc.edu/scPKD/) that can be used to identify cross- and intra-model changes in gene expression, guiding researchers to new therapeutic targets for treating PKD.

Abstract Our facility changed antibody screening methods from a gel microcolumn–based test (ID-Micro Typing System Gel Test; Ortho Clinical Diagnostics, Inc., Raritan, NJ) to an automated solid-phase test (Galileo/Capture-R Ready-Screen [I and II], Immucor, Inc., Norcross, GA). To determine whether detection rates for commonly encountered clinically significant red blood cell antibodies differed as a consequence of this change, preimplementation and postimplementation antibody identification records were retrospectively reviewed. A statistically significant difference in the percentage of positive screening tests during the gel microcolumn testing period (73,903 total screens, 1.56% confirmed positive) versus the solid-phase screening period (80,242 total screens, 1.81% confirmed positive; p < 0.0002) was observed. The number of antibodies to K identified was significantly lower with solid phase than with gel (27% decrease; p = 0.004). It is unknown whether there is a statistical difference in delayed or hemolytic transfusion reaction rates as this was not evaluated. Immunohematology 2013;29:101–04.