Single-cell RNA-sequencing resolves self-antigen expression during mTEC development
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/53767 |
Resumo: | The crucial capability of T cells for discrimination between self and non-self peptides is based on negative selection of developing thymocytes by medullary thymic epithelial cells (mTECs). The mTECs purge autoreactive T cells by expression of cell-type specific genes referred to as tissue-restricted antigens (TRAs). Although the autoimmune regulator (AIRE) protein is known to promote the expression of a subset of TRAs, its mechanism of action is still not fully understood. The expression of TRAs that are not under the control of AIRE also needs further characterization. Furthermore, expression patterns of TRA genes have been suggested to change over the course of mTEC development. Herein we have used single-cell RNA-sequencing to resolve patterns of TRA expression during mTEC development. Our data indicated that mTEC development consists of three distinct stages, correlating with previously described jTEC, mTEChi and mTEClo phenotypes. For each subpopulation, we have identified marker genes useful in future studies. Aire-induced TRAs were switched on during jTEC-mTEC transition and were expressed in genomic clusters, while otherwise the subsets expressed largely overlapping sets of TRAs. Moreover, population-level analysis of TRA expression frequencies suggested that such differences might not be necessary to achieve efficient thymocyte selection. |
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Single-cell RNA-sequencing resolves self-antigen expression during mTEC developmentGene regulation in immune cellsTranscriptomicsScience & TechnologyThe crucial capability of T cells for discrimination between self and non-self peptides is based on negative selection of developing thymocytes by medullary thymic epithelial cells (mTECs). The mTECs purge autoreactive T cells by expression of cell-type specific genes referred to as tissue-restricted antigens (TRAs). Although the autoimmune regulator (AIRE) protein is known to promote the expression of a subset of TRAs, its mechanism of action is still not fully understood. The expression of TRAs that are not under the control of AIRE also needs further characterization. Furthermore, expression patterns of TRA genes have been suggested to change over the course of mTEC development. Herein we have used single-cell RNA-sequencing to resolve patterns of TRA expression during mTEC development. Our data indicated that mTEC development consists of three distinct stages, correlating with previously described jTEC, mTEChi and mTEClo phenotypes. For each subpopulation, we have identified marker genes useful in future studies. Aire-induced TRAs were switched on during jTEC-mTEC transition and were expressed in genomic clusters, while otherwise the subsets expressed largely overlapping sets of TRAs. Moreover, population-level analysis of TRA expression frequencies suggested that such differences might not be necessary to achieve efficient thymocyte selection.RM is supported by a PhD Fellowship from the Fundação para a Ciência e Tecnologia, Portugal (SFRH/ BD/51950/2012). XZ is supported by an Advanced Postdoc Mobility Fellowship from the Swiss National Science Foundation (SNSF, grant number P300P2_151352). Part of the work was performed during XZ’s visit to the Simons Institute for the Theory of Computing. TL is supported by the Academy of Finland (Decision 311081). The authors would like to thank Bee Ling Ng and the staff of the Cytometry Core Facility, and Stephan Lorenz and the staff of the Single Cell Genomics Core Facility for their contribution. Mark Lynch is acknowledged for technical assistance with the Fluidigm C1 platform. Mike Stubbington and Kylie James are acknowledged for revising the language of the manuscript. We thank Sarah Teichmann for help and discussions regarding the manuscript.info:eu-repo/semantics/publishedVersionNature Publishing GroupUniversidade do MinhoMiragaia, Ricardo J.Zhang, X.Gomes, TomásSvensson, V.Ilicic, T.Henriksson, J.Kar, G.Lönnberg, T.20182018-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/53767engMiragaia, Ricardo J.; Zhang, X.; Gomes, Tomás; Svensson, V.; Ilicic, T.; Henriksson, J.; Kar, G.; Lönnberg, T., Single-cell RNA-sequencing resolves self-antigen expression during mTEC development. Scientific Reports, 8(685), 20182045-23222045-232210.1038/s41598-017-19100-429330484http://www.nature.com/srep/index.htmlinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:17:13Zoai:repositorium.sdum.uminho.pt:1822/53767Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:09:47.477601Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Single-cell RNA-sequencing resolves self-antigen expression during mTEC development |
title |
Single-cell RNA-sequencing resolves self-antigen expression during mTEC development |
spellingShingle |
Single-cell RNA-sequencing resolves self-antigen expression during mTEC development Miragaia, Ricardo J. Gene regulation in immune cells Transcriptomics Science & Technology |
title_short |
Single-cell RNA-sequencing resolves self-antigen expression during mTEC development |
title_full |
Single-cell RNA-sequencing resolves self-antigen expression during mTEC development |
title_fullStr |
Single-cell RNA-sequencing resolves self-antigen expression during mTEC development |
title_full_unstemmed |
Single-cell RNA-sequencing resolves self-antigen expression during mTEC development |
title_sort |
Single-cell RNA-sequencing resolves self-antigen expression during mTEC development |
author |
Miragaia, Ricardo J. |
author_facet |
Miragaia, Ricardo J. Zhang, X. Gomes, Tomás Svensson, V. Ilicic, T. Henriksson, J. Kar, G. Lönnberg, T. |
author_role |
author |
author2 |
Zhang, X. Gomes, Tomás Svensson, V. Ilicic, T. Henriksson, J. Kar, G. Lönnberg, T. |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Miragaia, Ricardo J. Zhang, X. Gomes, Tomás Svensson, V. Ilicic, T. Henriksson, J. Kar, G. Lönnberg, T. |
dc.subject.por.fl_str_mv |
Gene regulation in immune cells Transcriptomics Science & Technology |
topic |
Gene regulation in immune cells Transcriptomics Science & Technology |
description |
The crucial capability of T cells for discrimination between self and non-self peptides is based on negative selection of developing thymocytes by medullary thymic epithelial cells (mTECs). The mTECs purge autoreactive T cells by expression of cell-type specific genes referred to as tissue-restricted antigens (TRAs). Although the autoimmune regulator (AIRE) protein is known to promote the expression of a subset of TRAs, its mechanism of action is still not fully understood. The expression of TRAs that are not under the control of AIRE also needs further characterization. Furthermore, expression patterns of TRA genes have been suggested to change over the course of mTEC development. Herein we have used single-cell RNA-sequencing to resolve patterns of TRA expression during mTEC development. Our data indicated that mTEC development consists of three distinct stages, correlating with previously described jTEC, mTEChi and mTEClo phenotypes. For each subpopulation, we have identified marker genes useful in future studies. Aire-induced TRAs were switched on during jTEC-mTEC transition and were expressed in genomic clusters, while otherwise the subsets expressed largely overlapping sets of TRAs. Moreover, population-level analysis of TRA expression frequencies suggested that such differences might not be necessary to achieve efficient thymocyte selection. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018 2018-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/53767 |
url |
http://hdl.handle.net/1822/53767 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Miragaia, Ricardo J.; Zhang, X.; Gomes, Tomás; Svensson, V.; Ilicic, T.; Henriksson, J.; Kar, G.; Lönnberg, T., Single-cell RNA-sequencing resolves self-antigen expression during mTEC development. Scientific Reports, 8(685), 2018 2045-2322 2045-2322 10.1038/s41598-017-19100-4 29330484 http://www.nature.com/srep/index.html |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Nature Publishing Group |
publisher.none.fl_str_mv |
Nature Publishing Group |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799132524697354240 |