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Gene expression variability across cells and species shapes innate immunity.
Hagai, Tzachi; Chen, Xi; Miragaia, Ricardo J; Rostom, Raghd; Gomes, Tomás; Kunowska, Natalia; Henriksson, Johan; Park, Jong-Eun; Proserpio, Valentina; Donati, Giacomo; Bossini-Castillo, Lara; Vieira Braga, Felipe A; Naamati, Guy; Fletcher, James; Stephenson, Emily; Vegh, Peter; Trynka, Gosia; Kondova, Ivanela; Dennis, Mike; Haniffa, Muzlifah; Nourmohammad, Armita; Lässig, Michael; Teichmann, Sarah A.
Afiliação
  • Hagai T; Wellcome Sanger Institute, Cambridge, UK. tzachi@ebi.ac.uk.
  • Chen X; EMBL- European Bioinformatics Institute, Cambridge, UK. tzachi@ebi.ac.uk.
  • Miragaia RJ; Wellcome Sanger Institute, Cambridge, UK.
  • Rostom R; Wellcome Sanger Institute, Cambridge, UK.
  • Gomes T; Centre of Biological Engineering, University of Minho, Braga, Portugal.
  • Kunowska N; Wellcome Sanger Institute, Cambridge, UK.
  • Henriksson J; EMBL- European Bioinformatics Institute, Cambridge, UK.
  • Park JE; Wellcome Sanger Institute, Cambridge, UK.
  • Proserpio V; Wellcome Sanger Institute, Cambridge, UK.
  • Donati G; Wellcome Sanger Institute, Cambridge, UK.
  • Bossini-Castillo L; Wellcome Sanger Institute, Cambridge, UK.
  • Vieira Braga FA; Department of Life Sciences and Systems Biology, University of Turin, Torino, Italy.
  • Naamati G; Italian Institute for Genomic Medicine (IIGM), Torino, Italy.
  • Fletcher J; Department of Life Sciences and Systems Biology, University of Turin, Torino, Italy.
  • Stephenson E; Molecular Biotechnology Center, University of Turin, Torino, Italy.
  • Vegh P; Wellcome Sanger Institute, Cambridge, UK.
  • Trynka G; Wellcome Sanger Institute, Cambridge, UK.
  • Kondova I; Open Targets, Wellcome Sanger Institute, Cambridge, UK.
  • Dennis M; EMBL- European Bioinformatics Institute, Cambridge, UK.
  • Haniffa M; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Nourmohammad A; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Lässig M; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Teichmann SA; Wellcome Sanger Institute, Cambridge, UK.
Nature ; 563(7730): 197-202, 2018 11.
Article em En | MEDLINE | ID: mdl-30356220
As the first line of defence against pathogens, cells mount an innate immune response, which varies widely from cell to cell. The response must be potent but carefully controlled to avoid self-damage. How these constraints have shaped the evolution of innate immunity remains poorly understood. Here we characterize the innate immune response's transcriptional divergence between species and variability in expression among cells. Using bulk and single-cell transcriptomics in fibroblasts and mononuclear phagocytes from different species, challenged with immune stimuli, we map the architecture of the innate immune response. Transcriptionally diverging genes, including those that encode cytokines and chemokines, vary across cells and have distinct promoter structures. Conversely, genes that are involved in the regulation of this response, such as those that encode transcription factors and kinases, are conserved between species and display low cell-to-cell variability in expression. We suggest that this expression pattern, which is observed across species and conditions, has evolved as a mechanism for fine-tuned regulation to achieve an effective but balanced response.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Especificidade de Órgãos / Especificidade da Espécie / Transcrição Gênica / Células / Evolução Molecular / Imunidade Inata Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Especificidade de Órgãos / Especificidade da Espécie / Transcrição Gênica / Células / Evolução Molecular / Imunidade Inata Idioma: En Ano de publicação: 2018 Tipo de documento: Article