Defining Patient-Level Molecular Heterogeneity in Psoriasis Vulgaris Based on Single-Cell Transcriptomics

Authors

Yale Liu
Hao Wang
Christopher Cook
Mark A Taylor
Jeffrey P North
Ashley Hailer
Yanhong Shou
Arsil Sadik
Esther Kim
Elizabeth Purdom
Jeffrey B Cheng
Raymond J Cho

Language

English

Publication Date

1-1-2022

Journal

Frontiers in Immunology

DOI

10.3389/fimmu.2022.842651

PMID

35958578

PMCID

PMC9360479

PubMedCentral® Posted Date

7-26-2022

PubMedCentral® Full Text Version

Post-print

Abstract

Identifying genetic variation underlying human diseases establishes targets for therapeutic development and helps tailor treatments to individual patients. Large-scale transcriptomic profiling has extended the study of such molecular heterogeneity between patients to somatic tissues. However, the lower resolution of bulk RNA profiling, especially in a complex, composite tissue such as the skin, has limited its success. Here we demonstrate approaches to interrogate patient-level molecular variance in a chronic skin inflammatory disease, psoriasis vulgaris, leveraging single-cell RNA-sequencing of CD45+ cells isolated from active lesions. Highly psoriasis-specific transcriptional abnormalities display greater than average inter-individual variance, nominating them as potential sources of clinical heterogeneity. We find that one of these chemokines, CXCL13, demonstrates significant correlation with severity of lesions within our patient series. Our analyses also establish that genes elevated in psoriatic skin-resident memory T cells are enriched for programs orchestrating chromatin and CDC42-dependent cytoskeleton remodeling, specific components of which are distinctly correlated with and against Th17 identity on a single-cell level. Collectively, these analyses describe systematic means to dissect cell type- and patient-level differences in cutaneous psoriasis using high-resolution transcriptional profiles of human inflammatory disease.

Keywords

Humans, Psoriasis, RNA, Skin, Th17 Cells, Transcriptome, single-cell RNA-sequencing, psoriasis vulgaris, heterogeneity, cytoskeleton, chromatin

Published Open-Access

no

Recommended Citation

Liu, Yale; Wang, Hao; Cook, Christopher; et al., "Defining Patient-Level Molecular Heterogeneity in Psoriasis Vulgaris Based on Single-Cell Transcriptomics" (2022). Staff and Researcher Publications. 25.
https://digitalcommons.library.tmc.edu/clinic_pub/25