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Prediction of cellular targets in diabetic kidney diseases with single-cell transcriptomic analysis of db/db mouse kidneys

Abstract

Diabetic kidney disease is the leading cause of impaired kidney function, albuminuria, and renal replacement therapy (dialysis or transplantation), thus placing a large burden on health-care systems. This urgent event requires us to reveal the molecular mechanism of this disease to develop more efficacious treatment. Herein, we reported single-cell RNA sequencing analyses in kidneys of db/db mouse, an animal model for type 2 diabetes and diabetic kidney disease. We first analyzed the hub genes expressed differentially in the single cell resolution transcriptome map of the kidneys. Then we figured out the communication among the renal and immune cells in the kidneys. Data from this report may provide novel information for better understanding the cell-specific targets involved in the aetiologia of type 2 diabetic kidney disease and for cell communication and signaling between renal cells and immune cells of this complex disease.

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Data availability

The datasets and computer code produced in this study are available in the following databases: Our scRNA-Seq data: Sequence Read Archive PRJNA749372 (https://www.ncbi.nlm.nih.gov/sra/PRJNA749372). In order to provide scRNA profiles from this study, we have constructed an interactive shiny-app as a web tool for your visit (http://biomamba.com:34038/DKD.data.set/). Referenced scRNA-Seq data: Gene Expression Omnibus GSE107585 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE107585). Other original contributions are included in this article, including tables, figures, and supplementary material.

Abbreviations

AGEs:

Advanced glycation end products

ALH:

Ascending loop of Henle

BCAA:

Branched-chain amino acids

CD-IC:

Collecting duct intercalated cell

CD-PC:

Collecting duct principal cell

CR:

Creatinine

DCT:

Distal convoluted tubule

DEGs:

Differentially expressed genes

DLH:

Descending loop of Hence

DKD:

Diabetic kidney disease

DM:

Diabetes mellitus

EERA:

Erythropoietin receptor

EnC:

Endothelial cell

ESKF:

End-stage kidney failure

GO:

Gene ontology

IDF:

International Diabetes Federation

KAP:

Kidney androgen-regulated protein

KEGG:

Kyoto encyclopedia of genes and genomes

Mac:

Macrophage

mtRNA:

Mitochondrial RNA

OPN:

Osteopontin

PCT:

Proximal convoluted tubule

PTCs:

Proximal epithelial tubular cells

RAAS:

Renin–angiotensin–aldosterone system

RSCEP:

Renal stromal cells except PTCs

scRNA-seq:

Single-cell RNA sequencing

SNN:

Shared nearest neighbor

STZ:

Streptozotocin

T1D:

Type 1 diabetes

T2D:

Type 2 diabetes

tSNE:

T-distributed stochastic neighbor embedding

UA:

Urinary albuminuria

UAER:

Urinary albumin excretion rate

UMAP:

Uniform manifold approximation and projection

UMI:

Unique molecular identifiers

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Acknowledgements

The authors wish to thank Dr. Katalin Susztak for her positive agreement and valuable discussion.

Funding

This study was supported by the start grants from China Pharmaceutical University (CPU20180815 HFG), the Cooperation Research Project (CPU20200228 HFG).

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Contributions

Conceived and designed the experiments: Harvest F. Gu; Data acquisition and analysis: Chenhua Wu, Yingjun Tao, Nan Li, Jingjin Fei; Laboratory management: Yurong Wang; Data interpretation: Jie Wu, and Harvest F. Gu; Manuscript preparation and revision: Chenhua Wu and Harvest F. Gu; All authors agreed and approved the final version of manuscript.

Corresponding authors

Correspondence to Jie Wu or Harvest F. Gu.

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Wu, C., Tao, Y., Li, N. et al. Prediction of cellular targets in diabetic kidney diseases with single-cell transcriptomic analysis of db/db mouse kidneys. J. Cell Commun. Signal. (2022). https://doi.org/10.1007/s12079-022-00685-z

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  • DOI: https://doi.org/10.1007/s12079-022-00685-z

Keywords

  • Diabetes
  • Diabetic kidney disease
  • End-stage renal disease
  • Proximal epithelial tubular cells
  • Single-cell RNA sequencing