Kidney Week

Abstract: TH-PO0561

Multiome Analysis of In Utero Nephrogenesis Cessation in Nonhuman Primates

Session Information

• Development, Stem Cells, and Regenerative Medicine
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Development, Stem Cells, and Regenerative Medicine

• 600 Development, Stem Cells, and Regenerative Medicine

Authors

• Schuh, Meredith Posner, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States

Meredith Posner Schuh, MD, FASN

• Hilliard, Sylvia, Tulane University Department of Pediatrics, New Orleans, Louisiana, United States

Sylvia Hilliard, PhD

• Thorner, Konrad, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States

Konrad Thorner, MS

• Yarlagadda, Sunitha, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States

Sunitha Yarlagadda, MSc

• Potter, Andrew, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States

Andrew Potter, MS

• Stowers, Kaitlynn E, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States

Kaitlynn E Stowers, MSc

• Tortelote, Giovane G., Tulane University Department of Pediatrics, New Orleans, Louisiana, United States

Giovane G. Tortelote, MS, PhD

• Nakum, Cimran, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States

Cimran Nakum

• Thakkar, Kairavee, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States

Kairavee Thakkar, MS

• Salomonis, Nathan, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States

Nathan Salomonis, PhD

• El-Dahr, Samir S., Tulane University Department of Pediatrics, New Orleans, Louisiana, United States

Samir S. El-Dahr, MD

Background

Human nephrogenesis is completed prior to birth at 34-36 week gestation. We previously demonstrated age-dependent signatures within the nephron progenitor cells (NPC) from mid to late gestation. In this study, we investigated the changes in accessibility of genomic regulatory elements and gene expression at nephrogenesis cessation in the non-human primate model.

Methods

Paired single-cell ATAC and RNA (scATAC and scRNA) sequencing was performed on three cortically-enriched fetal rhesus kidneys from late-second trimester (n=2, pre-cessation) and third trimester (n=1, at time of nephrogenesis cessation). Nephron progenitor cells (NPCs) were filtered by EYA1^high/CDH1^low low signature. Gene expression matrix, peak calling, peak-to-gene linkages, and chromatin accessibility matrices were generated using ArchR and Signac.

Results

Paired scATAC and scRNA-seq of 14,088 rhesus cells were clustered to identify 20 transcriptionally distinct cell populations. Filtering the cells by EYA1^high/CDH1^low resulted in 1002 NPC, of which 906 were from second trimester and 96 from third trimester. We identified a decrease in accessibility of the SIX2 enhancer in third-trimester NPC compared to second trimester, and this finding was associated with decreased SIX2 RNA expression. We identified changes in gene score, motif, and gene expression matrices from second to third trimester, with shifts from SIX/BHLH/FOX to TEAD/HNF1/KLF motifs/gene scores at the time of cessation. Additionally, differential peak calling identified changes in WNT and SEMA peaks at the time of nephrogenesis cessation.

Conclusion

The rhesus macaque enables molecular studies of in utero primate nephrogenesis cessation. Our study supports conserved mechanisms of nephrogenesis cessation, as well as changes in chromatin accessibility not previously seen in the mouse. Future studies will focus on maintaining this signaling environment to promote nephron formation in preterm infants.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025jkecq6pe