Single-cell RNA-seq Analysis To Explore Bone-marrow Immune Landscape

Gunjan Dixit0, Di Yu1, Jiayu Wen0
(0) Australian National University
(1) University of Queensland

Find me on Wed Nov 25th, 1:30-2:50pm AEDT in Remo, table 78

Abstract
Bone marrow (BM) contains multiple immune cell subsets with critical functions and is considered an immune regulatory organ. It contains osteoclasts and immune cells fundamentally involved in physiological and pathological bone remodelling. In autoimmune diseases, inflammation can impair the BM niche, disturb hematopoietic and immune development, and induce osteoporosis. Specific cytokines exhibit pleiotropic effects on the immune system, and their discovery in the regulation of survival, differentiation and propagation of activated T cells paved the path for its direct clinical implications in immunotherapy. This project addresses the fundamental question of how low-dose of CytokineX modulates BM immune landscape by comprehensively mapping the therapy-induced changes using single-cell technologies. I analyzed the scRNA-seq data obtained from BM of CD45 cells of mice to identify different immune cell types and compared their expression across four experimental conditions- a control (sham), control treated with CytokineX (Sham+Treatment), ovariectomy-induced osteoporosis (OVX) and OVX treated with CytokineX (OVX+Treatment). The study reveals cellular heterogeneity in different experimental conditions and identifies rare cell type ILC2. Gene expression profiles of diseased and treated samples show a significant decrease in differentially expressed genes. Pathway analysis highlights important mechanisms like osteoclast differentiation being upregulated in the diseased samples whereas downregulated after the treatment with CytokineX explaining a potential role in inhibiting bone resorption during Osteoporosis.