Single-cell transcriptomic profiling reveals decreased ER Protein Reticulon3 drives the progression of renal fibrosis
Description
We delve into the consequences of Rtn3 protein deficiency in CKD by studying Rtn3-null-induced CKD mice. Our single-cell transcriptome data profiles 47,885 cells from the renal cortex region of healthy and Rtn3-null mice. We observed Rtn3 deficiency reshapes both the spatial architectures and the expression profiles across various cell types, mirroring the CKD characteristics. Meanwhile, Rtn3 deficiency leads to Lars2 overexpression, causing mitochondrial dysfunction and a subsequent rise in ROS levels, prompting renal epithelial cells to shift from a functional to a fibrogenic state, driving renal fibrosis. And Rtn3 deficiency drives the EndoMT process, exacerbating renal fibrosis in CKD. Lastly, Rtn3 deficiency disrupts cell-cell communications, which are important for proper kidney function, and potentially exacerbates CKD progression. In conclusion, Rtn3 protein deficiency leads to significant alterations in spatial architectures and molecular profiles for various cell types, and disrupts cell-cell communications. Our findings offer a holistic view of Rtn3 protein's intricate role in CKD and emphasize its potential therapeutic significance.
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We collected human transcriptomics data from two independent datasets[4,11]. The bulk mRNA profiling of 42 kidney transplant recipients at different stages was obtained from GSE126805. The processed CD10- cells, CD10+ cells, and human PDGFRβ+ cells data were obtained from the Zenodo data archive (https://zenodo.org/record/4059315, https://doi.org/10.5281/zenodo.4059315). Our processed scRNAseq datasets and the scripts for data preprocessing and analyzing are available https://github.com/alfredsguo/rtn3_null_ckd_project.