In:
Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-7-26)
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.
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2022.842651
DOI:
10.3389/fimmu.2022.842651.s001
DOI:
10.3389/fimmu.2022.842651.s002
DOI:
10.3389/fimmu.2022.842651.s003
DOI:
10.3389/fimmu.2022.842651.s004
DOI:
10.3389/fimmu.2022.842651.s005
DOI:
10.3389/fimmu.2022.842651.s006
DOI:
10.3389/fimmu.2022.842651.s007
DOI:
10.3389/fimmu.2022.842651.s008
DOI:
10.3389/fimmu.2022.842651.s009
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2606827-8
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