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:	Erich Horeth, Akinsola Oyelakin, Eun-Ah Christine Song, Monika Che, Jonathan Bard, Sangwon Min, Jeremy Kiripolsky, Jill M. Kramer, Satrajit Sinha, Rose-Anne Romano
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	primary Sjögren’s syndrome salivary glands RNA-sequencing single cell RNA-sequencing gene expression genomics Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/dc6e5442713e441cae4198893ed50266
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spelling	oai:doaj.org-article:dc6e5442713e441cae4198893ed502662021-12-01T11:42:08ZTranscriptomic and Single-Cell Analysis Reveals Regulatory Networks and Cellular Heterogeneity in Mouse Primary Sjögren’s Syndrome Salivary Glands1664-322410.3389/fimmu.2021.729040https://doaj.org/article/dc6e5442713e441cae4198893ed502662021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.729040/fullhttps://doaj.org/toc/1664-3224Sjögren’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.Erich HorethAkinsola OyelakinEun-Ah Christine SongMonika CheJonathan BardJonathan BardSangwon MinJeremy KiripolskyJill M. KramerSatrajit SinhaRose-Anne RomanoRose-Anne RomanoFrontiers Media S.A.articleprimary Sjögren’s syndromesalivary glandsRNA-sequencingsingle cell RNA-sequencinggene expressiongenomicsImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	primary Sjögren’s syndrome salivary glands RNA-sequencing single cell RNA-sequencing gene expression genomics Immunologic diseases. Allergy RC581-607
spellingShingle	primary Sjögren’s syndrome salivary glands RNA-sequencing single cell RNA-sequencing gene expression genomics Immunologic diseases. Allergy RC581-607 Erich Horeth Akinsola Oyelakin Eun-Ah Christine Song Monika Che Jonathan Bard Jonathan Bard Sangwon Min Jeremy Kiripolsky Jill M. Kramer Satrajit Sinha Rose-Anne Romano Rose-Anne Romano Transcriptomic and Single-Cell Analysis Reveals Regulatory Networks and Cellular Heterogeneity in Mouse Primary Sjögren’s Syndrome Salivary Glands
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.
format	article
author	Erich Horeth Akinsola Oyelakin Eun-Ah Christine Song Monika Che Jonathan Bard Jonathan Bard Sangwon Min Jeremy Kiripolsky Jill M. Kramer Satrajit Sinha Rose-Anne Romano Rose-Anne Romano
author_facet	Erich Horeth Akinsola Oyelakin Eun-Ah Christine Song Monika Che Jonathan Bard Jonathan Bard Sangwon Min Jeremy Kiripolsky Jill M. Kramer Satrajit Sinha Rose-Anne Romano Rose-Anne Romano
author_sort	Erich Horeth
title	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_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_sort	transcriptomic and single-cell analysis reveals regulatory networks and cellular heterogeneity in mouse primary sjögren’s syndrome salivary glands
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/dc6e5442713e441cae4198893ed50266
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Transcriptomic and Single-Cell Analysis Reveals Regulatory Networks and Cellular Heterogeneity in Mouse Primary Sjögren’s Syndrome Salivary Glands

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