Activated B cells exhibit altered metabolic programs in Systemic sclerosis skin

Authors

• M Sahu
• R Lafyatis
• P Gourh

Abstract

Background
Systemic sclerosis (SSc) is a rare, chronic disease characterized by autoimmunity, vasculopathy and fibrosis. Here, we examine mitochondrial (mt) gene expression in SSc skin single cell RNA sequencing data and identify activated B cells as the major cell type.

Materials and methods
We analyzed skin single cell RNA expression profiles of 10 healthy individuals and 27 SSc patients using Seurat and identified different skin cell-types. We interrogated expression of 14 protein-coding mt genes. Differentially expressed genes were used to identify pathways/processes dysregulated in SSc. Metabolic gene expressions were imputed in each cell and were used to estimate cell-wise fluxome.

Results and discussion
We identified up-regulation of 10 mt-genes (p<0.05, Log2FC = +/- 0.25) in SSc B cell as compared to healthy individuals. These genes included ATP synthase (MT-ATP6), Cytochrome c oxidase (MT-CO1, MT-CO2, MT-CO3) and NADH dehydrogenase (MT-ND1, MT-ND2, MT-ND3, MT-ND4, MT-ND4L and MT-ND5). MT-ND3 was found to have a higher expression in different SSc skin cell-types as compared to controls. Pathway enrichment analysis identified major pathways involved in fulfilling metabolic/energy needs of SSc B cells. Up-regulation of B cell receptor signaling pathway was also seen in these SSc B cells. Sub-clustering of B cell identified increased number of activated B cells in SSc with higher mt-gene expression. This metabolically activated B cells seen in SSc, had an increased class-II HLA gene expression as well. Activated B cells were found to have high Deoxycytidine yield which could be potential target in SSc.

Scientific Focus Area: Computational Biology

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