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Abstract: TH-PO0323

Multispecies, Single-Cell, Multi-Omic Analysis Reveals the Mechanism of Podocyte Species Conserved Molecule GOLIM4

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

  • Chen, Qilin, Children's Hospital of Chongqing Medical University, Chongqing, Chongqing, China
  • Ye, Xinyi, Children's Hospital of Chongqing Medical University, Chongqing, Chongqing, China
  • Li, Shuying, Children's Hospital of Chongqing Medical University, Chongqing, Chongqing, China
  • Yang, Haiping, Children's Hospital of Chongqing Medical University, Chongqing, Chongqing, China
  • Qiu, Li, Children's Hospital of Chongqing Medical University, Chongqing, Chongqing, China
Background

The physiological processes of mammals require the kidney to exert ultrafiltration function, but there is a lack of conservation analysis of multiple species of kidney cells, and there is a lack of understanding and mechanism research on its conserved molecules and specific molecules.

Methods

We constructed a single-cell transcriptome (scRNA-seq) and single-cell chromatin accessibility (scATAC-seq) atlas covering human, pig, mouse, rat, and bat kidneys, revealing the species-conserved molecules of kidney cells in multiple species and the transcription and chromatin accessibility characteristics of human-specific molecules.

Results

The clusters in the scRNA-seq and scATAC-seq of human, pig, mouse, rat and bat kidneys were defined by classical marker molecules. In various species, classical molecules such as NPHS1 and NPHS2 in podocytes show a high peak state at the starting site, while PLA2R and PCOLCE2 only show a high peak state at the starting site of humans. Furthermore, we found that GOLIM4, which is closely related to the Golgi apparatus, showed a high level in podocytes of multiple species, both at the transcriptional level and chromatin accessibility level. The results of tissue fluorescence and histochemical staining confirmed that GOLIM4 was highly expressed in podocytes in human, rat and mouse kidneys, and co-localized with the Golgi marker molecule GM130. Through tissue staining of patients and disease models, we confirmed that GOLIM4 expression was significantly reduced in podocyte injury. The modeling of adriamycin in GOLIM4 knockout mice showed increased proteinuria and aggravated podocyte injury. Among them, TLN1, which directly interacts with GOLIM4, was significantly reduced in podocytes of GOLIM4 knockout mice, and ITGB1 associated with TLN1 was also reduced.

Conclusion

This research revealed that the differences in the molecular characteristics of kidney cells at the species level may be related to changes in chromatin accessibility. The conserved molecule GOLIM4 of podocyte Golgi species may play a key role in podocyte function through the GOLIM4-TLN1-ITGB1 pathway.