Nature · 2021

COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets.

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди

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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, Hether Tyler, Jané-Valbuena Judit, Leney-Greene Michael, Ma Hui, McCabe Cristin, McLoughlin Daniel E, Miller Eric M, Muus Christoph, Niemi Mari, Padera Robert, Pan Liuliu, Pant Deepti, Pe'er Carmel, Pfiffner-Borges Jenna, Pinto Christopher J, Plaisted Jacob, Reeves Jason, Ross Marty, Rudy Melissa, Rueckert Erroll H, Siciliano Michelle, Sturm Alexander, Todres Ellen, Waghray Avinash, Warren Sarah, Zhang Shuting, Zollinger Daniel R, Cosimi Lisa, Gupta Rajat M, Hacohen Nir, Hibshoosh Hanina, Hide Winston, Price Alkes L, Rajagopal Jayaraj, Tata Purushothama Rao, Riedel Stefan, Szabo Gyongyi, Tickle Timothy L, Ellinor Patrick T, Hung Deborah, Sabeti Pardis C, Novak Richard, Rogers Robert, Ingber Donald E, Jiang Z Gordon, Juric Dejan, Babadi Mehrtash, Farhi Samouil L, Izar Benjamin, Stone James R, Vlachos Ioannis S, Solomon Isaac H, Ashenberg Orr, Porter Caroline B M, Li Bo, Shalek Alex K, Villani Alexandra-Chloé, Rozenblatt-Rosen Orit, Regev Aviv

Аннотация

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.

COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets.

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Аннотация

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