ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

ASN / Education & Meetings / Kidney Week /

Please note that you are viewing an archived section from 2022 and some content may be unavailable. To unlock all content for 2022, please visit the archives.

Abstract: FR-OR32

Human Kidney Multimodal Single Cell and Spatial Transcriptomics Atlas Identify Key Cell Types and Pathways for Diabetic Kidney Disease

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Abedini, Amin, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Ma, Ziyuan, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Frederick, Julia, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Devalaraja-Narashimha, Kishor B., Cardiovascular, Renal and Fibrosis Research, Regeneron Pharmaceuticals Inc, Tarrytown, New York, United States
  • Morton, Lori, Cardiovascular, Renal and Fibrosis Research, Regeneron Pharmaceuticals Inc, Tarrytown, New York, United States
  • Kalra, Gurmannat, Research and Development, GSK, Collegeville, Pennsylvania, United States
  • Hu, Erding, Research and Development, GSK, Collegeville, Pennsylvania, United States
  • Sarov-Blat, Lea, Research and Development, GSK, Collegeville, Pennsylvania, United States
  • Boustany, Carine, Department of Cardiometabolic Diseases Research, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut, United States
  • Guarnieri, Paolo, Department of Cardiometabolic Diseases Research, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut, United States
  • Liles, John T., Department of Biology, Gilead Sciences, Foster City, California, United States
  • Karihaloo, Anil K., Novo Nordisk Research Center Seattle, Inc, Seattle, Washington, United States
  • Yan, Hanying, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Coleman, Kyle P., University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Hu, Jian, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Zhang, Qihuang, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Palmer, Matthew, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Li, Mingyao, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Susztak, Katalin, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Background

Diabetic kidney disease (DKD) is responsible for more than half of all end stage renal disease in the US, yet disease driving cell types and pathways are poorly defined. Innovative single cell tools can define transcriptomics, gene regulation or even spatial gene expression at single cell resolution.

Methods

We generated single cell and single nuclear gene expression (scRNA-seq, snRNA-seq) and single nuclear assay of open chromatin (snATAC-seq) datasets for 66 (34 healthy and 32 CKD/DKD) samples capturing 0.5 million cells. Furthermore, we generated high-quality spatial gene expression datasets for healthy and DKD kidneys. The data was complemented with bulk RNA-seq, clinical and histological information available for 298 human kidney samples.

Results

Our high-quality kidney single cell atlas captured 40 main and more than 100 cell subtypes or cell states, including epithelial, endothelial, immune and stromal cells. Using a combination of snRNA and spatial transcriptomics analyses, we successfully mapped all cell types and states back to their spatial location in healthy and diseased kidneys. Our results highlighted the key role of proximal tubule, immune, and stromal cells in disease development. We identified different localization patterns of different cell types, including a novel interaction between stromal, immune cells and injured tubule cells in fibrosis. Our analyses defined a gene signature pattern for injury niches, which could also accurately classify a cohort of 298 tubule bulk RNA-seq into subsets based on eGFR and renal fibrosis.

Conclusion

Our comprehensive human kidney single cell and spatial atlas define new pathways and gene signatures for DKD, and a valuable resource for the community to identify potential new therapeutic targets, pathways and cell types in kidney diseases.

Funding

  • Commercial Support – GSK, Regeneron, Boehringer, Gilead, Novo Nordisk