Single-cell RNA Sequencing of Peripheral Blood Mononuclear Cells in Patients with Single Ventricle/Hypoplastic Left Heart Syndrome
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background
Single ventricle and hypoplastic left heart syndrome (SV/HLHS) patients require lifelong medical monitoring and management to address potential complications and optimize their health. The consequence of SV/HLHS had detrimental effects on multiple organ systems, including on peripheral blood mononuclear cells (PBMCs) and can weaken the immune system, exacerbating the risk of infection and various cardiovascular complications.
Methods
Using single-cell RNA sequencing (scRNA-seq), we studied PBMCs from 33 pediatric patients (10 females and 23 males) with SV/HLHS. By a pair-wide study design, the SV/HLHS patients were compared to 33 controls without heart diseases.
Results
Four cell types account for the top 62% cumulative importance of disease effects on gene expression in different cell types, i.e., [T cells, CD4+, Th1/17], [T cells, CD4+, TFH], [NK cells], and [T cells, CD4+, Th2]. Significant sex differences were observed in [T cells, CD4+, TFH], with less prominent effects in female patients. A total of 6659 genes in different cell types were significantly differentially expressed (DE). Hierarchical clustering by WGCNA analysis of the DE genes revealed that DE genes in NK cells are most closely related to those in SV/HLHS. A total of 822 genes showed cell specific DE with opposite directions in different cell types, highlighting overrepresented MYC and IFN-γ activity in T cell and NK cell populations, as well as underrepresentation in monocytes and Treg cells.
Conclusion
This study elucidates the complex transcriptome landscape in PBMCs in patients with SV/HLHS, emphasizing the differential impacts on various cell types. New insights are gained into the precise modulation of MYC and IFN-γ activity in SV/HLHS, which may help balance immune responses and reduce harmful inflammation, and promote effective tissue repair and infection control.
