Single cell transcriptomics-based comparison of regenerative repair vs. fibrotic response in chronic kidney disease

• Applicant: Dr. Michael S. Balzer
• Subject Area: Nephrology
• Term: from 2019 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 431088862

Fibrosis is the histological correlate of chronic kidney disease (CKD), which affects 1 in 10 people worldwide. While on the one hand the kidney has the ability to regenerate and repair following acute kidney injury, on the other there is also a maladaptive path towards kidney fibrosis, resulting in epithelial atrophy, inflammatory cell influx, myofibroblast accumulation and collagen deposition. Genomic studies relying on RNA sequencing have been widely and successfully used to better understand CKD development. However, a major obstacle of bulk RNA sequencing was that its sensitivity is limited to identify gene expression changes only in predominant cell populations or cell heterogeneity changes, whereas rare cell populations (such as progenitors) or opposing gene expression changes in different cell types are omitted. Single cell sequencing brings with it the ability to monitor genome-wide gene regulation in thousands of single cells in one single experiment, enabling us to discover novel, rare cell types and states, and trace the origin and fate of cells. The primary goal of this project is to identify distinct cell types, cell-type specific transcriptomes and cell composition changes for both regenerative kidney repair and maladaptive injury response as in kidney fibrosis/CKD. State-of-the-art transcriptomic analysis will be used to demonstrate expected differences between kidney repair and fibrosis states following the same insult (ischemia).

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professorin Dr. Katalin Susztak, Ph.D.