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Kidney Week

Abstract: FR-PO971

Single-Cell Transcriptomic Profiling of Kidney Fibrosis Identifies a Novel Fibroblast Marker and Putative Disease Target

Session Information

  • CKD: Pathobiology - I
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2203 CKD (Non-Dialysis): Mechanisms


  • Rudman-Melnick, Valeria, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Adam, Mike, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Devarajan, Prasad, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States

Group or Team Name

  • Devarajan lab

Fibrosis is a key underlying process in CKD, resulting in renal parenchymal remodeling and progressive functional decline with prominent mortality. Cellular identity of renal fibrosis along with putative molecular targets regulating it remain elusive.


We used 10x Chromium and Drop-seq platforms to create transcriptomic profiles of two clinically relevant unilateral inshemia/reperfusion (UIR) and ureter obstruction (UUO) murine models of renal fibrosis. Moreover, we used primary human in vitro model of epithelial-to-mesenchymal transition (EMT) to identify novel putative CKD targets.


Using scRNA-seq, we observed several novel injury induced kidney cell clusters, including three distinctive stromal populations, and identified Gucy1a3 as a novel specific marker of renal fibroblasts. Both CKD models exhibited robust nephrogenic program reactivation and intercellular communications, particularly between activated fibroblasts and tubular epithelial cells (TECs). We revealed elevation of fibrogenic factors in the injured TECs, including Ahnak which we previously reported in AKI. We showed that AHNAK ablation causes elevation of EMT and downregulation of epithelial markers in primary human renal proximal tubular epithelial cells (RPTECs) with and without TGFβ (Figure 1). We also found that p38, p42/44, pAKT, BMP and MMP signaling underlies AHNAK effects in primary human in vitro model of EMT.


Our novel findings, including identification of Gucy1a3 as a specific kidney fibroblast marker and Ahnak as an injury target, might improve our understanding and approach to halting kidney fibrosis.

Figure 1. AHNAK ablation exacerbates EMT in primary human RPTECs. (A) and (F) AHNAK and ZO1 ICC, RPTECs. (B-D) Western blots for AHNAK, EMT and epithelial markers. (E) qPCR of Ecad and Ggt1. **pValue ≤ 0.01, *** ≤ 0.001, **** ≤ 0.0001, one-way ANOVA (C, D), t test (E).


  • NIDDK Support