ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

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

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: SA-OR074

Single Cell Landscapes of Human Kidney in Health and Disease

Session Information

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Vernon, Katherine Anne, Broad Institute, Cambridge, Massachusetts, United States
  • Subramanian, Ayshwarya, Broad Institute, Cambridge, Massachusetts, United States
  • Zhou, Yiming, Brigham and Women''s Hospital/Harvard Medical School, Boston, Massachusetts, United States
  • Weins, Astrid, Brigham & Women's Hospital, Boston, Massachusetts, United States
  • Greka, Anna, Harvard Medical School, Boston, Massachusetts, United States
Background

Chronic kidney disease is a global health concern and yet therapies to prevent or halt its progression remain scarce. The emergence of single-cell genomics has provided the opportunity to simultaneously characterize the transcriptomic profile of thousands of individual cells and their respective states, revealing differences previously hidden by bulk analyses. As part of an effort to expand knowledge of regional cell identity, function and diversity within the kidney as a basis to understand and treat disease, we set out to catalog the cell types in different regions of the kidney and the perturbations seen with disease. The detailed identification of cellular landscapes across a variety of kidney diseases using single-cell and single-nucleus RNA sequencing (RNA-seq), aims to illuminate therapeutic targets for the development of precision therapies.

Methods

Macroscopically normal, fresh kidney tissue from patients undergoing tumor nephrectomies and frozen tissue sampled from diagnostic renal biopsies, were used to generate single cell and nuclei suspensions respectively. Droplet-based single-cell or single-nucleus RNA-seq libraries were prepared, amplified by PCR and sequenced. Established computational analytical techniques and a panel of canonical marker genes curated in our laboratory, were used to cluster the different cell types present.

Results

We identified heterogeneous cell populations characteristic of expected kidney cell types and detected regional differences predicted from known anatomy. The changing landscape in the setting of disease was revealed by changes such as the presence of additional immune cell populations.

Conclusion

Having established single-cell dissociation and single-nuclei isolation protocols for fresh and frozen human kidney specimens, this study represents an unprecedented cell mapping effort to identify disease-specific pathophysiological mechanisms and reveal novel therapeutic opportunities. The ability to prevent the potentially inexorable decline to kidney failure would represent a major advance and revolutionize the outlook for renal patients worldwide.

Funding

  • Private Foundation Support