A single-cell map for the transcriptomic signatures of peripheral blood mononuclear cells in end-stage renal disease.
Nephrol Dial Transplant
; 36(4): 599-608, 2021 03 29.
Article
in En
| MEDLINE
| ID: mdl-31883338
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Leukocytes, Mononuclear
/
Gene Expression Regulation
/
Single-Cell Analysis
/
Transcriptome
/
Kidney Failure, Chronic
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Nephrol Dial Transplant
Journal subject:
NEFROLOGIA
/
TRANSPLANTE
Year:
2021
Document type:
Article
Affiliation country:
China