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

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 lo...

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Autores principales: Liu, Yale, Wang, Hao, Cook, Christopher, Taylor, Mark A., North, Jeffrey P., Hailer, Ashley, Shou, Yanhong, Sadik, Arsil, Kim, Esther, Purdom, Elizabeth, Cheng, Jeffrey B., Cho, Raymond J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360479/
https://www.ncbi.nlm.nih.gov/pubmed/35958578
http://dx.doi.org/10.3389/fimmu.2022.842651
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author Liu, Yale
Wang, Hao
Cook, Christopher
Taylor, Mark A.
North, Jeffrey P.
Hailer, Ashley
Shou, Yanhong
Sadik, Arsil
Kim, Esther
Purdom, Elizabeth
Cheng, Jeffrey B.
Cho, Raymond J.
author_facet Liu, Yale
Wang, Hao
Cook, Christopher
Taylor, Mark A.
North, Jeffrey P.
Hailer, Ashley
Shou, Yanhong
Sadik, Arsil
Kim, Esther
Purdom, Elizabeth
Cheng, Jeffrey B.
Cho, Raymond J.
author_sort Liu, Yale
collection PubMed
description 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.
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spelling pubmed-93604792022-08-10 Defining Patient-Level Molecular Heterogeneity in Psoriasis Vulgaris Based on Single-Cell Transcriptomics Liu, Yale Wang, Hao Cook, Christopher Taylor, Mark A. North, Jeffrey P. Hailer, Ashley Shou, Yanhong Sadik, Arsil Kim, Esther Purdom, Elizabeth Cheng, Jeffrey B. Cho, Raymond J. Front Immunol Immunology 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. Frontiers Media S.A. 2022-07-26 /pmc/articles/PMC9360479/ /pubmed/35958578 http://dx.doi.org/10.3389/fimmu.2022.842651 Text en Copyright © 2022 Liu, Wang, Cook, Taylor, North, Hailer, Shou, Sadik, Kim, Purdom, Cheng and Cho https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Liu, Yale
Wang, Hao
Cook, Christopher
Taylor, Mark A.
North, Jeffrey P.
Hailer, Ashley
Shou, Yanhong
Sadik, Arsil
Kim, Esther
Purdom, Elizabeth
Cheng, Jeffrey B.
Cho, Raymond J.
Defining Patient-Level Molecular Heterogeneity in Psoriasis Vulgaris Based on Single-Cell Transcriptomics
title Defining Patient-Level Molecular Heterogeneity in Psoriasis Vulgaris Based on Single-Cell Transcriptomics
title_full Defining Patient-Level Molecular Heterogeneity in Psoriasis Vulgaris Based on Single-Cell Transcriptomics
title_fullStr Defining Patient-Level Molecular Heterogeneity in Psoriasis Vulgaris Based on Single-Cell Transcriptomics
title_full_unstemmed Defining Patient-Level Molecular Heterogeneity in Psoriasis Vulgaris Based on Single-Cell Transcriptomics
title_short Defining Patient-Level Molecular Heterogeneity in Psoriasis Vulgaris Based on Single-Cell Transcriptomics
title_sort defining patient-level molecular heterogeneity in psoriasis vulgaris based on single-cell transcriptomics
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360479/
https://www.ncbi.nlm.nih.gov/pubmed/35958578
http://dx.doi.org/10.3389/fimmu.2022.842651
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