Single‐cell RNA‐seq with spatial transcriptomics to create an atlas of human diabetic kidney disease

Abstract

The worldwide prevalence of diabetes mellitus (DM) has rapidly increased over the past 30 years along with consequential increases in the prevalence of microvascular and macrovascular diabetes complications. 1-7 Among patients with type 1 or 2 DM, 30%-40% develop diabetic kidney disease (DKD), with ~50% subsequently progressing to end-stage kidney disease that is associated with a high mortality rate. [8][9][10][11] Several factors can enhance the pathogenetic pathways initiated and sustained in the kidney by elevated glucose levels in DKD. These include metabolic

Crosstalk among podocytes, glomerular endothelial cells and mesangial cells in diabetic kidney disease: an updated review

“…A study that explored cell-to-cell interactions and signaling networks within different kidney cell subsets, using ligand-receptor analysis, revealed stronger interactions between fibroblasts from individuals with DKD and various cell types such as proximal tubule cells, podocytes, and endothelial cells, in comparison to nondiabetic controls and individuals with diabetes but no kidney disease (DM samples) [ 136 ]. Importantly, these diverse cell interactions were primarily related to chemokines and were predominantly concentrated in fibroblasts, highlighting the close correlation between renal fibrosis and immune responses in the context of DKD [ 136 ].…”

“…• Limitations: Not mentioned. [ 136 , 209 ] Biomimetic systems in vitro Kidney organoid Kidney organoid: a self-organizing, three-dimensional aggregate of cells, derived from embryonic stem cells and induced pluripotent stem cells (iPSCs). A study developed the first diabetic kidney organoid model to explore the potential mechanisms underlying the increased disease severity in patients with COVID-19 and diabetes; • Advantages: It may be the first time to allow in vitro research on Proteinuria, to realize mechanism and preclinical research.…”

“…Future studies are required to unravel their interactions and unveil their roles in diabetic glomerular disease. ScRNA-seq analysis has facilitated the confirmation of specific markers and genes expressed in glomerular cells, leading to the identification of several new potential markers for glomerular cells in DKD [ 136 ].…”

New insights into the role of immunity and inflammation in diabetic kidney disease in the omics era

“…Nonetheless, single-cell studies have explored the landscape of immune cells in DKD tissues. Multiple single-cell RNA sequencing (scRNA-seq) studies have demonstrated the elevated proportion of immune cells during the progression of DKD ( 7 , 64 – 69 ). Chen et al.…”

“…The application of genomics and epigenetics techniques offers valuable insights into the immune- and inflammation-related genetic factors that contribute to the susceptibility of individuals to DKD ( 32 , 34 , 41 , 45 , 48 , 49 , 54 , 58 , 61 , 62 ). Transcriptomics provides a comprehensive perspective on the patterns of gene expression, thereby elucidating the immune- and inflammation-related molecular pathways implicated in DKD ( 64 , 65 , 73 ). Proteomics allows the identification of proteins that are intricately linked with immune responses and inflammation in DKD, shedding light on potential biomarkers and therapeutic targets for DKD ( 87 , 91 , 94 , 95 ).…”