Kidney Week

Abstract: TH-PO533

An Omnibus of Transcripts Integrated from More than One Million Nuclei and Cells of Patients with Kidney Diseases Provides Distinct Insights into Disease Mechanisms

Session Information

• Glomerular Diseases: Omics, Biomarkers, and Tools
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• McCown, Phillip J., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Phillip J. McCown, MS, PhD

• Otto, Edgar A., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Edgar A. Otto, PhD

• Fermin, Damian, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Damian Fermin, PhD

• Hartman, John R., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

John R. Hartman

• Alaba, Mathew Olakunle, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Mathew Olakunle Alaba, MS

• Larkina, Maria, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Maria Larkina, MS

• Arbit, Michael, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Michael Arbit

• Helmuth, Margaret, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Margaret Helmuth, MA

• Godfrey, Brad A., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Brad A. Godfrey, PhD

• Eddy, Sean, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Sean Eddy, PhD

• Mariani, Laura H., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Laura H. Mariani, MD, MS, FASN

• Naik, Abhijit S., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Abhijit S. Naik, MD, MPH, FASN

• Hoek, Maarten, Maze Therapeutics Inc, South San Francisco, California, United States

Maarten Hoek, PhD

• Satterfield, Terry, Maze Therapeutics Inc, South San Francisco, California, United States

Terry Satterfield, PhD

• Kretzler, Matthias, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Matthias Kretzler, MD

Group or Team Name

• NEPTUNE Consortium.

Background

Single nuclear RNA sequencing (snRNAseq) of biopsies affords insight to molecular and cellular pathways in kidneys. In the NEPTUNE consortium, biopsy samples of participants with nephrotic syndrome (NS) have been curated for snRNAseq. While small studies have provided insights using subsets of samples, an omnibus of transcriptional data from numerous samples may aid further discovery and research.

Methods

snRNAseq (n=11) and single cell RNA sequencing (n=47) from kidney biopsies from healthy living donors and transplant recipients in the Michigan HKTTA study were integrated with snRNAseq of 120 biopsies from patients with FSGS, MCD, IgAN, and other kidney diseases enrolled in the NEPTUNE Consortium to identify clusters of cells. Whole genome sequencing data from blood samples of 90 NEPTUNE participants were used to assess APOL1 genotype.

Results

Nuclei and cells (n=1,047,781) resolved into 28 clusters of kidney resident and non-resident cell types, including a novel cluster of transitioning parietal epithelial cells. APOL1 risk alleles were present in 90 participants. Among kidney cell types, we observed the strongest correlation between APOL1 mRNA levels and JAK-STAT activity in podocytes in participants with FSGS with at least one copy of the G1 APOL1 risk allele.

Conclusion

This Omnibus of CElls And Nuclei (OCEAN) from NEPTUNE participants with NS and IgAN is a large set of molecular and clinical data that allows unique analyses that can provide novel insights into mechanisms of kidney diseases

A UMAP of over 1 million nuclei and cells in OCEAN

Funding

• NIDDK Support – Maze Therapeutics