Identifying Mechanisms of Renal Repair

Key Personnel

Andrew McMahon (PI)
University of Southern California

• Andrew Ransick
  University of Southern California
• Jing Liu
  University of Southern California

Project Description

An improved understanding of renal repair mechanisms, and their limits, may enable the development of approaches to lower renal burden. With this long-term goal in sight, we will apply approaches to identify the transcriptional signatures of reparative cell types in a mouse model of acute kidney injury to identify signatures that underlie effective and non-effective renal repair. We will employ FACS to isolate nuclei of replicating, reparative renal tubular cell types expressing a genetically activated green fluorescent protein restricted to nephron nuclei, and EDU-labeling to identify the replicating component of nephron nuclei post-ischemia reperfusion injury (IRI). Single nuclear transcriptional profiling (NUC-seq) will be performed in each model at 72hrs and 28days after IRI to provide new insights into the diversity of cellular responses associated with different stages and different outcomes to renal injury. Key predictions will be followed up by secondary molecular analysis of tissue sections by quantitative PCR, in situ hybridization and immunostaining. Further, findings will be related to human kidney transplant injury through the analysis of existing RNA-seq data from protocol biopsies. Together these studies aim to provide new insights into individual cell actions in injury and repair of the mammalian nephron.