Transcriptional profiling of mouse proximal tubular epithelial cells during injury and repair

Proximal tubule has a remarkable capacity for repair after acute kidney injury. Whether dedifferentiation or a fixed progenitor population is responsible for this repair remains the subject of ongoing controversy. We have generated a novel genetic mouse model to address this question. We generated a Kim-1-GFPCreERt2 knockin mouse line (Kim1GCE) by homologous recombination. Kim-1 is expressed exclusively in dedifferentiated proximal tubule cells. We crossed this mouse line to the EGFP-L10a mouse line to perform Translating Ribosome Affinity Purification coupled with next generation sequencing (TRAP-seq) to identify the transcriptional signature of tubular epithelial cells during the course of injury and repair. TRAP-seq was performed in kidney samples at day 2, 7, and 14 after bilateral ischemia reperfusion injury and sham. Overall design: Bigenic Kim1-GCE; EGFPL10a heterozygous male mice (8-10 weeks old) received taxomifen 6 hours before and 24 hours after bilateral ischemia reperfusion injury. Kidneys were harvested at the designated time points for a total of four cohorts with 3 biological replicates in each group: sham, day 2, day 7, and day 14.