Single-cell RNA sequencing unraveled the expression heterogeneity of hematopoietic stem and progenitor cells and immune cell development dysregulation in childhood asthma

Abstract

Here, using single-cell RNA sequencing, we profile peripheral blood mononuclear cells (PBMCs) from three patients with onset asthma and four age-matched healthy controls to investigate the cellular etiology of childhood asthma. We find that very few differentially expressed genes (DEGs) in hematopoietic stem and progenitor cells (HSPCs) are common among three asthma cases, but the common ones are functionally related to S100A gene family. Furthermore, GO analyses show that the heterogeneous DEGs in HSPCs in three asthma cases can be clearly categorized into the biological processes of immunity and immune responses, which indicates that different DEGs converge on a common pathological base. The overall cellular expression profiles demonstrate that pro-inflammatory mediators and immunoglobulin receptors have a high expression level and interferon alpha induced protein has a low expression level in mononuclear macrophages of acute asthma. The cell developmental trajectories in three asthma cases exhibit an abnormal immune cell development pattern compared to the developmental trajectory in health control. T-cell development in acute asthma is especially dysregulated for three cases with three different T-cell branching pattern. We also find that the innate lymphoid cells (ILCs) in three asthma cases have a low expression level in housekeeping genes. Our scRNA-seq analyses for three asthma patients reveal a complex cellular etiology for childhood asthma and provide a new research direction for the comprehensive and systematic study of effector cells and key molecular mechanisms of childhood asthma.