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Abstract: PO0882

Single-Cell RNA Sequencing Reveals Subpopulation of PDGFRββ Pericytes as Fibroblast Precursor in Interstitial Kidney Fibrosis, and Smad Anchor for Receptor Activation Overexpression Modifies Their Fates

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 500 Development, Stem Cells, and Regenerative Medicine

Authors

  • Liang, Xiaoyan, Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, Illinois, United States
  • Dalal, Vidhi, Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, Illinois, United States
  • Schnaper, H. William, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Hayashida, Tomoko, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
Background

In last several ASN meetings, we showed that SARA plays a critical role for fibroblast precursor activation, and that overexpressing SARA in PDGFRβ+ pericytes prevents chemically-induced kidney fibrosis in interstitium. Here, we present our findings from single cell RNAseq analyses of PDGFRβ+ pericytes with or without fibrosis.

Methods

PDGFRβ-Cre; Z/EG; SARATg or WT mice that express GFP and SARA (in SARATg line) only in PDGFRβ+ cells were given aristolochic acid (AA, 10 mg/kg, i.p., 3x week for 3 weeks). After 3 more weeks, kidneys were harvested and digested with Liberase/DNAse I. GFP+ cells were flow sorted and subjected to scRNAseq. 2-3 samples from a group (WT or SARATg, and AA or control) were analyzed altogether by Seurat clustering, and subsequent inter-cluster analyses.

Results

Unsupervised analyses with Surat identified 30 clusters. Clusters characterized with differential expression of Apoe1 and C1a1 were dominant in cells isolated from healthy WT kidney, whereas clusters differentially expressing Kap and Cd74 became dominant in WT kidney treated with AA. This shift was abrogated in cells isolated from fibrotic SARATg kidney. RNA velocity analyses to reveal specific clusters that transition to fibroblasts are being analyzed.

Conclusion

These results implicate a sub-population of PDGFRβ+ pericytes are progenitors for fibroblasts in fibrosing kidney and genes identified that are differentially expressed could have therapeutic implication in treating kidney fibrosis.

Funding

  • NIDDK Support