| Literature DB >> 33915569 |
Toni M Delorey1, Carly G K Ziegler2,3,4,5,6,7, Graham Heimberg1, Rachelly Normand2,8,9,10,11, Yiming Yang1,8, Åsa Segerstolpe1, Domenic Abbondanza1, Stephen J Fleming12,13, Ayshwarya Subramanian1, Daniel T Montoro2, Karthik A Jagadeesh1, Kushal K Dey14, Pritha Sen2,8,15,16, Michal Slyper1, Yered H Pita-Juárez2,10,17,18,19, Devan Phillips1, Jana Biermann20,21, Zohar Bloom-Ackermann22, Nikolaos Barkas12, Andrea Ganna23,24, James Gomez22, Johannes C Melms20,21, Igor Katsyv25, Erica Normandin2,10, Pourya Naderi10,17,18, Yury V Popov10,26,27, Siddharth S Raju2,28,29, Sebastian Niezen10,26,27, Linus T-Y Tsai2,10,26,30,31, Katherine J Siddle2,32, Malika Sud1, Victoria M Tran22, Shamsudheen K Vellarikkal2,33, Yiping Wang20,21, Liat Amir-Zilberstein1, Deepak S Atri2,33, Joseph Beechem34, Olga R Brook35, Jonathan Chen2,36, Prajan Divakar34, Phylicia Dorceus1, Jesse M Engreitz2,37, Adam Essene26,30,31, Donna M Fitzgerald38, Robin Fropf34, Steven Gazal39, Joshua Gould1,12, John Grzyb40, Tyler Harvey1, Jonathan Hecht10,17, Tyler Hether34, Judit Jané-Valbuena1, Michael Leney-Greene2, Hui Ma1,8, Cristin McCabe1, Daniel E McLoughlin38, Eric M Miller34, Christoph Muus2,41, Mari Niemi23, Robert Padera40,42,43, Liuliu Pan34, Deepti Pant26,30,31, Carmel Pe'er1, Jenna Pfiffner-Borges1, Christopher J Pinto16,38, Jacob Plaisted40, Jason Reeves34, Marty Ross34, Melissa Rudy2, Erroll H Rueckert34, Michelle Siciliano40, Alexander Sturm22, Ellen Todres1, Avinash Waghray44,45, Sarah Warren34, Shuting Zhang22, Daniel R Zollinger34, Lisa Cosimi46, Rajat M Gupta2,33, Nir Hacohen2,9,47, Hanina Hibshoosh25, Winston Hide10,17,18,19, Alkes L Price14, Jayaraj Rajagopal38, Purushothama Rao Tata48, Stefan Riedel10,17, Gyongyi Szabo2,10,26, Timothy L Tickle1,12, Patrick T Ellinor49, Deborah Hung22,50,51, Pardis C Sabeti2,32,52,53,54, Richard Novak55, Robert Rogers26,56, Donald E Ingber41,55,57, Z Gordon Jiang10,26,27, Dejan Juric16,38, Mehrtash Babadi12,13, Samouil L Farhi1, Benjamin Izar20,21,58,59, James R Stone36, Ioannis S Vlachos60,61,62,63,64, Isaac H Solomon40, Orr Ashenberg1, Caroline B M Porter1, Bo Li1,8,16, Alex K Shalek65,66,67,68,69,70,71,72,73,74,75, Alexandra-Chloé Villani76,77,78,79, Orit Rozenblatt-Rosen80,81, Aviv Regev82,83,84,85.
Abstract
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.Entities:
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Year: 2021 PMID： 33915569 PMCID： PMC8919505 DOI： 10.1038/s41586-021-03570-8
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 69.504