Ting Luo1, Fengping Zheng2, Kang Wang2, Yong Xu2, Huixuan Xu2, Wenxi Shen2, Chengxin Zhu2, Xinzhou Zhang2, Weiguo Sui3, Donge Tang2, Lianghong Yin1, Yong Dai1,2. 1. Institute of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China. 2. The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China. 3. Department of Nephrology, Guangxi Key Laboratory of Metabolic Diseases Research, Guilin NO. 924 Hospital, Guilin, China.
Abstract
BACKGROUND: Immune aberrations in end-stage renal disease (ESRD) are characterized by systemic inflammation and immune deficiency. The mechanistic understanding of this phenomenon remains limited. METHODS: We generated 12 981 and 9578 single-cell transcriptomes of peripheral blood mononuclear cells (PBMCs) that were pooled from 10 healthy volunteers and 10 patients with ESRD by single-cell RNA sequencing. Unsupervised clustering and annotation analyses were performed to cluster and identify cell types. The analysis of hallmark pathway and regulon activity was performed in the main cell types. RESULTS: We identified 14 leukocytic clusters that corresponded to six known PBMC types. The comparison of cells from ESRD patients and healthy individuals revealed multiple changes in biological processes. We noticed an ESRD-related increase in inflammation response, complement cascade and cellular metabolism, as well as a strong decrease in activity related to cell cycle progression in relevant cell types in ESRD. Furthermore, a list of cell type-specific candidate transcription factors (TFs) driving the ESRD-associated transcriptome changes was identified. CONCLUSIONS: We generated a distinctive, high-resolution map of ESRD-derived PBMCs. These results revealed cell type-specific ESRD-associated pathways and TFs. Notably, the pooled sample analysis limits the generalization of our results. The generation of larger single-cell datasets will complement the current map and drive advances in therapies that manipulate immune cell function in ESRD.
BACKGROUND: Immune aberrations in end-stage renal disease (ESRD) are characterized by systemic inflammation and immune deficiency. The mechanistic understanding of this phenomenon remains limited. METHODS: We generated 12 981 and 9578 single-cell transcriptomes of peripheral blood mononuclear cells (PBMCs) that were pooled from 10 healthy volunteers and 10 patients with ESRD by single-cell RNA sequencing. Unsupervised clustering and annotation analyses were performed to cluster and identify cell types. The analysis of hallmark pathway and regulon activity was performed in the main cell types. RESULTS: We identified 14 leukocytic clusters that corresponded to six known PBMC types. The comparison of cells from ESRDpatients and healthy individuals revealed multiple changes in biological processes. We noticed an ESRD-related increase in inflammation response, complement cascade and cellular metabolism, as well as a strong decrease in activity related to cell cycle progression in relevant cell types in ESRD. Furthermore, a list of cell type-specific candidate transcription factors (TFs) driving the ESRD-associated transcriptome changes was identified. CONCLUSIONS: We generated a distinctive, high-resolution map of ESRD-derived PBMCs. These results revealed cell type-specific ESRD-associated pathways and TFs. Notably, the pooled sample analysis limits the generalization of our results. The generation of larger single-cell datasets will complement the current map and drive advances in therapies that manipulate immune cell function in ESRD.