Single-Cell Sequencing Finds New Target for Acute Kidney Injury Treatment
Summary
The subject of the present discourse concerns a scientific investigation of a particular form of renal injury, termed "acute kidney injury" or AKI. In this investigation, the authors utilized a sophisticated method known as single-cell RNA sequencing to discern a multiplicity of immune cells known as mononuclear phagocytic cells or MPCs, which are implicated in the processes of inflammation and tissue repair that occur after AKI. The inquiry yielded the discovery of a specific subset of MPCs which expressed proteins denoted as S100a8/S100a9, and which served as the initiators and propagators of the inflammatory response within the renal system. In addition, the study evidenced that pharmacologically hindering these proteins could result in the reduction of inflammation, amelioration of renal function, and prevention of long-term complications, including fibrosis. The article, therefore, advanced the notion that this particular subset of MPCs represents a promising target for therapeutic intervention in cases of AKI.
Research Criteria
The research idea is to identify the disease-associated macrophage subsets during the acute phase of ischemia reperfusion injury induced AKI (IRI-AKI) and uncover their functional states, markers, and potential molecular regulators at single-cell resolution. The research idea is based on the hypothesis that macrophages have a critical impact on whether the kidney injury is resolved or progressed to subsequent chronic kidney disease.
Fig.1 Experimental design. (Yao, 2022)
Sample Type
Cells from mouse blood, kidney, and spleen.
Result—Mononuclear Phagocyte Atlas at Single-Cell Resolution in Mice with IRI-AKI
They performed a time series of scRNA-seq on sorted cells collected from the kidney, blood, and spleen of mice before and after 45 minutes of unilateral kidney ischemia followed by reperfusion for 1 and 3 days to gain a comprehensive understanding of the potential origins and dynamic features of MPCs in the acute injury stage of AKI. There were a total of 80,829 cells that passed quality control and were divided into 26 clusters. In an effort to track the possible ontogenesis of renal mesenchymal progenitor cells (MPCs) subsequent to injury, the research team devised three distinct gene sets, characterized by the monocytes/macrophages present in the kidney, blood, and spleen during homeostasis. The gene sets were founded on genes expressed in cells that were extracted from the three organs under normal conditions, and other typical genes previously identified in the literature. Upon conducting a transcriptomic similarity analysis, it was revealed that 74.69% of macrophages present in the kidney on day 1 post-injury bore resemblance to monocytes sourced from the blood sample taken during homeostasis. This correspondence is indicative of the fact that a significant majority of macrophages, which made an appearance in the injured kidney during the acute injury stage, were derived from blood monocytes. The percentage reduced to 19.86% on day 3 after injury.
Fig.2 Single cell transcriptomics profiling of MPCs. (Yao, 2022)
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Reference
- Yao, W.; et al. Single cell RNA sequencing identifies a unique inflammatory macrophage subset as a druggable target for alleviating acute kidney injury. Advanced Science. 2022, 9(12): 2103675.
