Your browser doesn't support javascript.
loading
Spatially resolved deconvolution of the fibrotic niche in lung fibrosis.
Eyres, Michael; Bell, Joseph A; Davies, Elizabeth R; Fabre, Aurelie; Alzetani, Aiman; Jogai, Sanjay; Marshall, Ben G; Johnston, David A; Xu, Zijian; Fletcher, Sophie V; Wang, Yihua; Marshall, Gayle; Davies, Donna E; Offer, Emily; Jones, Mark G.
Afiliación
  • Eyres M; Medicines Discovery Catapult, Alderley Park, Cheshire, UK.
  • Bell JA; Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK.
  • Davies ER; Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK; Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton,
  • Fabre A; Department of Histopathology, St. Vincent's University Hospital & UCD School of Medicine, University College Dublin, Dublin, Ireland.
  • Alzetani A; NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK; University Hospital Southampton, Southampton, UK.
  • Jogai S; NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK; University Hospital Southampton, Southampton, UK.
  • Marshall BG; NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK; University Hospital Southampton, Southampton, UK.
  • Johnston DA; Biomedical Imaging Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
  • Xu Z; Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK; Institute for Life Sciences, University of Southampton, Southampton, UK.
  • Fletcher SV; NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK; University Hospital Southampton, Southampton, UK.
  • Wang Y; NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK; Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK; Institute for Life Sciences, University of Southampton, Southampton, UK.
  • Marshall G; Medicines Discovery Catapult, Alderley Park, Cheshire, UK.
  • Davies DE; Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK; Institute for Life Sciences, University of Southampton, Southampton, UK.
  • Offer E; Medicines Discovery Catapult, Alderley Park, Cheshire, UK.
  • Jones MG; Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK; Institute for Life Sciences, University of Southampton, Southampton, UK. Electronic address: mark.jones@
Cell Rep ; 40(7): 111230, 2022 08 16.
Article en En | MEDLINE | ID: mdl-35977489
A defining pathological feature of human lung fibrosis is localized tissue heterogeneity, which challenges the interpretation of transcriptomic studies that typically lose spatial information. Here we investigate spatial gene expression in diagnostic tissue using digital profiling technology. We identify distinct, region-specific gene expression signatures as well as shared gene signatures. By integration with single-cell data, we spatially map the cellular composition within and distant from the fibrotic niche, demonstrating discrete changes in homeostatic and pathologic cell populations even in morphologically preserved lung, while through ligand-receptor analysis, we investigate cellular cross-talk within the fibrotic niche. We confirm findings through bioinformatic, tissue, and in vitro analyses, identifying that loss of NFKB inhibitor zeta in alveolar epithelial cells dysregulates the TGFß/IL-6 signaling axis, which may impair homeostatic responses to environmental stress. Thus, spatially resolved deconvolution advances understanding of cell composition and microenvironment in human lung fibrogenesis.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fibrosis Pulmonar Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cell Rep Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fibrosis Pulmonar Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cell Rep Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos