Dataset Information

Single-Cell Spatial Transcriptomics Unveils Platelet-Fueled Cycling Macrophages for Kidney Fibrosis.

ABSTRACT: With the increasing incidence of kidney diseases, there is an urgent need to develop therapeutic strategies to combat post-injury fibrosis. Immune cells, including platelets, play a pivotal role in this repair process, primarily through their released cytokines. However, the specific role of platelets in kidney injury and subsequent repair remains underexplored. Here, the detrimental role of platelets in renal recovery following ischemia/reperfusion injury and its contribution to acute kidney injury to chronic kidney disease transition is aimed to investigated. In this study, it is shown that depleting platelets accelerates injury resolution and significantly reduces fibrosis. Employing advanced single-cell and spatial transcriptomic techniques, macrophages as the primary mediators modulated by platelet signals is identified. A novel subset of macrophages, termed "cycling M2", which exhibit an M2 phenotype combined with enhanced proliferative activity is uncovered. This subset emerges in the injured kidney during the resolution phase and is modulated by platelet-derived thrombospondin 1 (THBS1) signaling, acquiring profibrotic characteristics. Conversely, targeted inhibition of THBS1 markedly downregulates the cycling M2 macrophage, thereby mitigating fibrotic progression. Overall, this findings highlight the adverse role of platelet THBS1-boosted cycling M2 macrophages in renal injury repair and suggest platelet THBS1 as a promising therapeutic target for alleviating inflammation and kidney fibrosis.

SUBMITTER: Liu J

PROVIDER: S-EPMC11304276 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Single-Cell Spatial Transcriptomics Unveils Platelet-Fueled Cycling Macrophages for Kidney Fibrosis.

Liu Jun J Zheng Bo B Cui Qingya Q Zhu Yu Y Chu Likai L Geng Zhi Z Mao Yiming Y Wan Lin L Cao Xu X Xiong Qianwei Q Guo Fujia F Yang David C DC Hsu Ssu-Wei SW Chen Ching-Hsien CH Yan Xiangming X

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20240605 29

With the increasing incidence of kidney diseases, there is an urgent need to develop therapeutic strategies to combat post-injury fibrosis. Immune cells, including platelets, play a pivotal role in this repair process, primarily through their released cytokines. However, the specific role of platelets in kidney injury and subsequent repair remains underexplored. Here, the detrimental role of platelets in renal recovery following ischemia/reperfusion injury and its contribution to acute kidney in ...[more]

PMID: 38838052

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Project description:BackgroundBiliary atresia (BA) is a devastating inflammatory and fibrosing cholangiopathy of neonates with unknown aetiology. We aim to investigate the relationship between these two main characteristics.MethodsSingle-cell RNA sequencing and spatial transcriptomics were performed on liver samples from a cohort of 14 objects (BA: n = 6; control: n = 8). We conducted data integration and cell-type annotation based on gene expression profiling. Furthermore, we identified fibrosis-related immune cells according to their spatial locations, GO and KEGG analysis. Finally, SPOTlight and CIBERSORTx were used to deconvolute ST data and microarray data of the GSE46960 cohorts, respectively.ResultsImmune subpopulations inhabiting the 'fibrotic niche' (areas of scarring), comprising 'intermediate' CD14++ CD16+ monocytes, scar-associated macrophages, natural killer T cells, transitional B cells and FCN3+ neutrophils were identified. GO and KEGG analyses showed that pathways including 'positive regulation of smooth muscle cell/fibroblast proliferation' and 'positive regulation of/response to VEGFR/VEGF/EGFR/FGF' were enriched in these cell types. Interactions analysis showed that communication among 'FGF_FGFR', 'RPS19-C5AR1', 'CD74_COPA/MIF/APP' and 'TNFRSF1A/B_GRN' was extensive. Finally, the results of deconvolution for ST data and microarray data validated that the proportions of certain identified fibrosis-related cell types we identified were increased in BA.DiscussionFibrosis is an important feature of BA, in which the immune system plays an important role. Our work reveals the subpopulations of immune cells enriched in the fibrotic niche of BA liver, as well as key related pathways and molecules; some are highlighted for the first time in liver fibrosis. These newly identified interactions might partly explain why the rate of liver fibrosis occurs much faster in BA than in other liver diseases.ConclusionOur study revealed the molecular, cellular and spatial immune microenvironment of the fibrotic niche of BA.

Dataset Information

Single-Cell Spatial Transcriptomics Unveils Platelet-Fueled Cycling Macrophages for Kidney Fibrosis.

Publications

Single-Cell Spatial Transcriptomics Unveils Platelet-Fueled Cycling Macrophages for Kidney Fibrosis.

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