Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.
Christoph Muus,Malte D Luecken,Gökcen Eraslan,Lisa Sikkema,Avinash Waghray,Graham Heimberg,Yoshihiko Kobayashi,Eeshit Dhaval Vaishnav,Eeshit Dhaval Vaishnav,Ayshwarya Subramanian,Christopher Smillie,Karthik A. Jagadeesh,Elizabeth Thu Duong,Evgenij Fiskin,Elena Torlai Triglia,Meshal Ansari,Peiwen Cai,Brian M. Lin,Justin Buchanan,Sijia Chen,Jian Shu,Adam L. Haber,Adam L. Haber,Hattie Chung,Daniel T. Montoro,Taylor Adams,Hananeh Aliee,Samuel J. Allon,Samuel J. Allon,Samuel J. Allon,Zaneta Andrusivova,Ilias Angelidis,Orr Ashenberg,Kevin Bassler,Christophe Bécavin,Inbal Benhar,Joseph Bergenstråhle,Ludvig Bergenstråhle,Liam Bolt,Emelie Braun,Linh T. Bui,Steven Callori,Mark Chaffin,Evgeny Chichelnitskiy,Joshua Chiou,Thomas M. Conlon,Michael S. Cuoco,Anna S E Cuomo,Marie Deprez,Grant Duclos,Denise Fine,David S. Fischer,Shila Ghazanfar,Astrid Gillich +53 more
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In this paper, cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues was assessed.Abstract:
Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.read more
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Mechanisms of SARS-CoV-2 entry into cells.
TL;DR: In this article, structural and cellular foundations for understanding the multistep SARS-CoV-2 entry process, including S protein synthesis, S protein structure, conformational transitions necessary for association of the spike (S) protein with ACE2, engagement of the receptor-binding domain of the S protein with ACS, proteolytic activation of S protein, endocytosis and membrane fusion are provided.
Journal ArticleDOI
COVID-19 and the human innate immune system.
TL;DR: In this article, a conceptual framework for the interaction of the human innate immune system with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was provided to link the clinical observations with experimental findings that have been made during the first year of the pandemic.
Journal ArticleDOI
COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets.
Toni Delorey,Carly G. K. Ziegler,Graham Heimberg,Rachelly Normand,Yiming Yang,Yiming Yang,Asa Segerstolpe,Domenic Abbondanza,Stephen J. Fleming,Ayshwarya Subramanian,Daniel T. Montoro,Karthik A. Jagadeesh,Kushal K. Dey,Pritha Sen,Michal Slyper,Yered Pita-Juárez,Devan Phillips,Jana Biermann,Zohar Bloom-Ackermann,Nikolaos Barkas,Andrea Ganna,Andrea Ganna,James Gomez,Johannes C. Melms,Igor Katsyv,Erica Normandin,Erica Normandin,Pourya Naderi,Pourya Naderi,Yury Popov,Yury Popov,Siddharth S. Raju,Siddharth S. Raju,Sebastian Niezen,Sebastian Niezen,Linus T.-Y. Tsai,Katherine J. Siddle,Katherine J. Siddle,Malika Sud,Victoria M. Tran,Shamsudheen K. Vellarikkal,Shamsudheen K. Vellarikkal,Yiping Wang,Liat Amir-Zilberstein,Deepak Atri,Deepak Atri,Joseph M. Beechem,Olga R. Brook,Jonathan H. Chen,Jonathan H. Chen,Prajan Divakar,Phylicia Dorceus,Jesse M. Engreitz,Jesse M. Engreitz,Adam Essene,Donna M. Fitzgerald,Robin Fropf,Steven Gazal,Joshua Gould,John Grzyb,Tyler Harvey,Jonathan L. Hecht,Jonathan L. Hecht,Tyler Hether,Judit Jané-Valbuena,Michael Leney-Greene,Hui Ma,Hui Ma,Cristin McCabe,Daniel E. McLoughlin,Eric M. Miller,Christoph Muus,Christoph Muus,Mari Niemi,Robert F. Padera,Robert F. Padera,Robert F. Padera,Liuliu Pan,Deepti Pant,Carmel Pe’er,Jenna Pfiffner-Borges,Christopher J. Pinto,Jacob Plaisted,Jason Reeves,Marty Ross,Melissa Rudy,Erroll H. Rueckert,Michelle Siciliano,Alexander Sturm,Ellen Todres,Avinash Waghray,Sarah Warren,Shuting Zhang,Daniel R. Zollinger,Lisa A. Cosimi,Rajat M. Gupta,Rajat M. Gupta,Nir Hacohen,Nir Hacohen,Hanina Hibshoosh,Winston Hide,Alkes L. Price,Jayaraj Rajagopal,Purushothama Rao Tata,Stefan Riedel,Stefan Riedel,Gyongyi Szabo,Gyongyi Szabo,Gyongyi Szabo,Timothy L. Tickle,Patrick T. Ellinor,Deborah T. Hung,Deborah T. Hung,Pardis C. Sabeti,Richard M. Novak,Robert S. Rogers,Robert S. Rogers,Donald E. Ingber,Donald E. Ingber,Donald E. Ingber,Z. Gordon Jiang,Z. Gordon Jiang,Dejan Juric,Mehrtash Babadi,Samouil L. Farhi,Benjamin Izar,James R. Stone,Ioannis S. Vlachos,Isaac H. Solomon,Orr Ashenberg,Caroline B. M. Porter,Bo Li,Bo Li,Alex K. Shalek,Alexandra-Chloé Villani,Orit Rozenblatt-Rosen,Orit Rozenblatt-Rosen,Aviv Regev +137 more
TL;DR: In this article, single-cell analysis of lung, heart, kidney and liver autopsy samples shows the molecular and cellular changes and immune response resulting from severe SARS-CoV-2 infection.
Journal ArticleDOI
A molecular single-cell lung atlas of lethal COVID-19.
Johannes C. Melms,Jana Biermann,Huachao Huang,Yiping Wang,Ajay Nair,Somnath Tagore,Igor Katsyv,André F. Rendeiro,Amit Dipak Amin,Denis Schapiro,Denis Schapiro,Chris J. Frangieh,Chris J. Frangieh,Adrienne M. Luoma,Aveline Filliol,Yinshan Fang,Hiranmayi Ravichandran,Mariano G. Clausi,George A. Alba,Meri Rogava,Sean W. Chen,Patricia Ho,Daniel T. Montoro,Daniel T. Montoro,Adam E. Kornberg,Arnold Han,Mathieu F. Bakhoum,Niroshana Anandasabapathy,Mayte Suárez-Fariñas,Samuel F. Bakhoum,Yaron Bram,Alain C. Borczuk,Xinzheng V. Guo,Jay H. Lefkowitch,Charles C. Marboe,Stephen M. Lagana,Armando Del Portillo,Emily J. Tsai,Emmanuel Zorn,Glen S. Markowitz,Robert F. Schwabe,Robert E. Schwartz,Olivier Elemento,Anjali Saqi,Hanina Hibshoosh,Jianwen Que,Benjamin Izar +46 more
TL;DR: In this paper, the authors performed single-nucleus RNA sequencing of about 116,000 nuclei from the lungs of nineteen individuals who died of COVID-19 and underwent rapid autopsy and seven control individuals.
Posted ContentDOI
The SARS-CoV-2 variant, Omicron, shows rapid replication in human primary nasal epithelial cultures and efficiently uses the endosomal route of entry
Thomas P. Peacock,Jonathan Brown,Jie-Nan Zhou,Nazia Thakur,Joseph Newman,Ruthiran Kugathasan,Ksenia Sukhova,Myrsini Kaforou,Dalan Bailey,Wendy S. Barclay +9 more
TL;DR: It is shown Omicron replicates rapidly in human primary airway cultures, more so even than the previously dominant variant of concern, Delta, and is posited to be more infectious at lower exposure doses, and resulting in enhanced intrinsic transmissibility.
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