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COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets.
Delorey, Toni M; Ziegler, Carly G K; Heimberg, Graham; Normand, Rachelly; Yang, Yiming; Segerstolpe, Åsa; Abbondanza, Domenic; Fleming, Stephen J; Subramanian, Ayshwarya; Montoro, Daniel T; Jagadeesh, Karthik A; Dey, Kushal K; Sen, Pritha; Slyper, Michal; Pita-Juárez, Yered H; Phillips, Devan; Biermann, Jana; Bloom-Ackermann, Zohar; Barkas, Nikolaos; Ganna, Andrea; Gomez, James; Melms, Johannes C; Katsyv, Igor; Normandin, Erica; Naderi, Pourya; Popov, Yury V; Raju, Siddharth S; Niezen, Sebastian; Tsai, Linus T-Y; Siddle, Katherine J; Sud, Malika; Tran, Victoria M; Vellarikkal, Shamsudheen K; Wang, Yiping; Amir-Zilberstein, Liat; Atri, Deepak S; Beechem, Joseph; Brook, Olga R; Chen, Jonathan; Divakar, Prajan; Dorceus, Phylicia; Engreitz, Jesse M; Essene, Adam; Fitzgerald, Donna M; Fropf, Robin; Gazal, Steven; Gould, Joshua; Grzyb, John; Harvey, Tyler; Hecht, Jonathan.
Afiliação
  • Delorey TM; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Ziegler CGK; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Heimberg G; Program in Health Sciences & Technology, Harvard Medical School and Massachusetts Institute of Technology, Boston, MA, USA.
  • Normand R; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Yang Y; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Segerstolpe Å; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Abbondanza D; Harvard Graduate Program in Biophysics, Harvard University, Cambridge, MA, USA.
  • Fleming SJ; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Subramanian A; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Montoro DT; Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Jagadeesh KA; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Dey KK; Harvard Medical School, Boston, MA, USA.
  • Sen P; Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Slyper M; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Pita-Juárez YH; Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Phillips D; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Biermann J; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Bloom-Ackermann Z; Data Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Barkas N; Precision Cardiology Laboratory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Ganna A; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Gomez J; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Melms JC; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Katsyv I; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA.
  • Normandin E; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Naderi P; Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Popov YV; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Raju SS; Department of Medicine, Harvard Medical School, Boston, MA, USA.
  • Niezen S; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Tsai LT; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Siddle KJ; Harvard Medical School, Boston, MA, USA.
  • Sud M; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Tran VM; Harvard Medical School Initiative for RNA Medicine, Boston, MA, USA.
  • Vellarikkal SK; Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Wang Y; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Amir-Zilberstein L; Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA.
  • Atri DS; Columbia Center for Translational Immunology, New York, NY, USA.
  • Beechem J; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Brook OR; Data Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Chen J; Institute for Molecular Medicine Finland, Helsinki, Finland.
  • Divakar P; Analytical & Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Dorceus P; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Engreitz JM; Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA.
  • Essene A; Columbia Center for Translational Immunology, New York, NY, USA.
  • Fitzgerald DM; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.
  • Fropf R; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Gazal S; Harvard Medical School, Boston, MA, USA.
  • Gould J; Harvard Medical School, Boston, MA, USA.
  • Grzyb J; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Harvey T; Harvard Medical School Initiative for RNA Medicine, Boston, MA, USA.
  • Hecht J; Harvard Medical School, Boston, MA, USA.
Nature ; 595(7865): 107-113, 2021 07.
Article em En | MEDLINE | ID: mdl-33915569
COVID-19, which is caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple organ failure1-4, but little is known about its pathophysiology. Here we generated single-cell atlases of 24 lung, 16 kidney, 16 liver and 19 heart autopsy tissue samples and spatial atlases of 14 lung samples from donors who died of COVID-19. Integrated computational analysis uncovered substantial remodelling in the lung epithelial, immune and stromal compartments, with evidence of multiple paths of failed tissue regeneration, including defective alveolar type 2 differentiation and expansion of fibroblasts and putative TP63+ intrapulmonary basal-like progenitor cells. Viral RNAs were enriched in mononuclear phagocytic and endothelial lung cells, which induced specific host programs. Spatial analysis in lung distinguished inflammatory host responses in lung regions with and without viral RNA. Analysis of the other tissue atlases showed transcriptional alterations in multiple cell types in heart tissue from donors with COVID-19, and mapped cell types and genes implicated with disease severity based on COVID-19 genome-wide association studies. Our foundational dataset elucidates the biological effect of severe SARS-CoV-2 infection across the body, a key step towards new treatments.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: SARS-CoV-2 / COVID-19 / Rim / Fígado / Pulmão / Miocárdio Limite: Aged80 Idioma: En Revista: Nature Ano de publicação: 2021 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: SARS-CoV-2 / COVID-19 / Rim / Fígado / Pulmão / Miocárdio Limite: Aged80 Idioma: En Revista: Nature Ano de publicação: 2021 Tipo de documento: Article