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Transcriptomic and Single-Cell Analysis Reveals Regulatory Networks and Cellular Heterogeneity in Mouse Primary Sjögren’s Syndrome Salivary Glands

Sjögren’s Syndrome (SS) is a chronic autoimmune disease of unknown etiology which primarily affects the salivary and lacrimal glands resulting in the loss of secretory function. Treatment options for SS have been hampered due to the lack of a better understanding of the underlying gene regulatory ci...

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Autores principales: Horeth, Erich, Oyelakin, Akinsola, Song, Eun-Ah Christine, Che, Monika, Bard, Jonathan, Min, Sangwon, Kiripolsky, Jeremy, Kramer, Jill M., Sinha, Satrajit, Romano, Rose-Anne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8666453/
https://www.ncbi.nlm.nih.gov/pubmed/34912329
http://dx.doi.org/10.3389/fimmu.2021.729040
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author Horeth, Erich
Oyelakin, Akinsola
Song, Eun-Ah Christine
Che, Monika
Bard, Jonathan
Min, Sangwon
Kiripolsky, Jeremy
Kramer, Jill M.
Sinha, Satrajit
Romano, Rose-Anne
author_facet Horeth, Erich
Oyelakin, Akinsola
Song, Eun-Ah Christine
Che, Monika
Bard, Jonathan
Min, Sangwon
Kiripolsky, Jeremy
Kramer, Jill M.
Sinha, Satrajit
Romano, Rose-Anne
author_sort Horeth, Erich
collection PubMed
description Sjögren’s Syndrome (SS) is a chronic autoimmune disease of unknown etiology which primarily affects the salivary and lacrimal glands resulting in the loss of secretory function. Treatment options for SS have been hampered due to the lack of a better understanding of the underlying gene regulatory circuitry and the interplay between the myriad pathological cellular states that contribute to salivary gland dysfunction. To better elucidate the molecular nature of SS, we have performed RNA-sequencing analysis of the submandibular glands (SMG) of a well-established primary Sjögren’s Syndrome (pSS) mouse model. Our comprehensive examination of global gene expression and comparative analyses with additional SS mouse models and human datasets, have identified a number of important pathways and regulatory networks that are relevant in SS pathobiology. To complement these studies, we have performed single-cell RNA sequencing to examine and identify the molecular and cellular heterogeneity of the diseased cell populations of the mouse SMG. Interrogation of the single-cell transcriptomes has shed light on the diversity of immune cells that are dysregulated in SS and importantly, revealed an activated state of the salivary gland epithelial cells that contribute to the global immune mediated responses. Overall, our broad studies have not only revealed key pathways, mediators and new biomarkers, but have also uncovered the complex nature of the cellular populations in the SMG that are likely to drive the progression of SS. These newly discovered insights into the underlying molecular mechanisms and cellular states of SS will better inform targeted therapeutic discoveries.
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spelling pubmed-86664532021-12-14 Transcriptomic and Single-Cell Analysis Reveals Regulatory Networks and Cellular Heterogeneity in Mouse Primary Sjögren’s Syndrome Salivary Glands Horeth, Erich Oyelakin, Akinsola Song, Eun-Ah Christine Che, Monika Bard, Jonathan Min, Sangwon Kiripolsky, Jeremy Kramer, Jill M. Sinha, Satrajit Romano, Rose-Anne Front Immunol Immunology Sjögren’s Syndrome (SS) is a chronic autoimmune disease of unknown etiology which primarily affects the salivary and lacrimal glands resulting in the loss of secretory function. Treatment options for SS have been hampered due to the lack of a better understanding of the underlying gene regulatory circuitry and the interplay between the myriad pathological cellular states that contribute to salivary gland dysfunction. To better elucidate the molecular nature of SS, we have performed RNA-sequencing analysis of the submandibular glands (SMG) of a well-established primary Sjögren’s Syndrome (pSS) mouse model. Our comprehensive examination of global gene expression and comparative analyses with additional SS mouse models and human datasets, have identified a number of important pathways and regulatory networks that are relevant in SS pathobiology. To complement these studies, we have performed single-cell RNA sequencing to examine and identify the molecular and cellular heterogeneity of the diseased cell populations of the mouse SMG. Interrogation of the single-cell transcriptomes has shed light on the diversity of immune cells that are dysregulated in SS and importantly, revealed an activated state of the salivary gland epithelial cells that contribute to the global immune mediated responses. Overall, our broad studies have not only revealed key pathways, mediators and new biomarkers, but have also uncovered the complex nature of the cellular populations in the SMG that are likely to drive the progression of SS. These newly discovered insights into the underlying molecular mechanisms and cellular states of SS will better inform targeted therapeutic discoveries. Frontiers Media S.A. 2021-11-29 /pmc/articles/PMC8666453/ /pubmed/34912329 http://dx.doi.org/10.3389/fimmu.2021.729040 Text en Copyright © 2021 Horeth, Oyelakin, Song, Che, Bard, Min, Kiripolsky, Kramer, Sinha and Romano 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
Horeth, Erich
Oyelakin, Akinsola
Song, Eun-Ah Christine
Che, Monika
Bard, Jonathan
Min, Sangwon
Kiripolsky, Jeremy
Kramer, Jill M.
Sinha, Satrajit
Romano, Rose-Anne
Transcriptomic and Single-Cell Analysis Reveals Regulatory Networks and Cellular Heterogeneity in Mouse Primary Sjögren’s Syndrome Salivary Glands
title Transcriptomic and Single-Cell Analysis Reveals Regulatory Networks and Cellular Heterogeneity in Mouse Primary Sjögren’s Syndrome Salivary Glands
title_full Transcriptomic and Single-Cell Analysis Reveals Regulatory Networks and Cellular Heterogeneity in Mouse Primary Sjögren’s Syndrome Salivary Glands
title_fullStr Transcriptomic and Single-Cell Analysis Reveals Regulatory Networks and Cellular Heterogeneity in Mouse Primary Sjögren’s Syndrome Salivary Glands
title_full_unstemmed Transcriptomic and Single-Cell Analysis Reveals Regulatory Networks and Cellular Heterogeneity in Mouse Primary Sjögren’s Syndrome Salivary Glands
title_short Transcriptomic and Single-Cell Analysis Reveals Regulatory Networks and Cellular Heterogeneity in Mouse Primary Sjögren’s Syndrome Salivary Glands
title_sort transcriptomic and single-cell analysis reveals regulatory networks and cellular heterogeneity in mouse primary sjögren’s syndrome salivary glands
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8666453/
https://www.ncbi.nlm.nih.gov/pubmed/34912329
http://dx.doi.org/10.3389/fimmu.2021.729040
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