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| 1 | Discriminating mild from critical COVID-19 by innate and adaptive immune single-cell profiling of bronchoalveolar lavages显示文摘How the innate and adaptive host immune system miscommunicate to worsen COVID-19 immunopathology has not been fully elucidated.Here,we perform single-cell deep-immune profiling of bronchoalveolar lavage(BAL)samples from 5 patients with mild and 26 with critical COVID-19 in comparison to BALs from non-COVID-19 pneumonia and normal lung.We use pseudotime inference to build T-cell and monocyte-to-macrophage trajectories and model gene expression changes along them.In mild COVID-19,CD8^(+)resident-memory(TRM)and CD4^(+)T-helper-17(T_(H17))cells undergo active(presumably antigen-driven)expansion towards the end of the trajectory,and are characterized by good effector functions,while in critical COVID-19 they remain more naïve.Vice versa,CD4^(+)T-cells with T-helper-1 characteristics(TH1-like)and CD8^(+)T-cells expressing exhaustion markers(T_(EX)-like)are enriched halfway their trajectories in mild COVID-19,where they also exhibit good effector functions,while in critical COVID-19 they show evidence of inflammation-associated stress at the end of their trajectories.Monocyte-to-macrophage trajectories show that chronic hyperinflammatory monocytes are enriched in critical COVID-19,while alveolar macrophages,otherwise characterized by anti-inflammatory and antigen-presenting characteristics,are depleted.In critical COVID-19,monocytes contribute to an ATP-purinergic signaling-inflammasome footprint that could enable COVID-19 associated fibrosis and worsen disease-severity.Finally,viral RNA-tracking reveals infected lung epithelial cells,and a significant proportion of neutrophils and macrophages that are involved in viral clearance. | Els Wauters Pierre Van Mol Abhishek Dinkarnath Garg Sander Jansen Yannick Van Herck Lore Vanderbeke Ayse Bassez Bram Boeckx Bert Malengier-Devlies Anna Timmerman Thomas Van Brussel Tina Van Buyten Rogier Schepers Elisabeth Heylen Dieter Dauwe Christophe Dooms Jan Gunst Greet Hermans Philippe Meersseman Dries Testelmans Jonas Yserbyt Sabine Tejpar Walter De Wever Patrick Matthys CONTAGIOUS collaborators Johan Neyts Joost Wauters Junbin Qian Diether Lambrechts | 2021 | Cell Research2021，31，3： | 11 |
| 2 | A pan-cancer blueprint of the heterogeneous tumor microenvironment revealed by single-cell profiling显示文摘The stromal compartment of the tumor microenvironment consists of a heterogeneous set of tissue-resident and tumor-infiltrating cells,which are profoundly moulded by cancer cells.An outstanding question is to what extent this heterogeneity is similar between cancers affecting different organs.Here,we profile 233,591 single cells from patients with lung,colorectal,ovary and breast cancer(n=36)and construct a pan-cancer blueprint of stromal cell heterogeneity using different single-cell RNA and protein-based technologies.We identify 68 stromal cell populations,of which 46 are shared between cancer types and 22 are unique.We also characterise each population phenotypically by highlighting its marker genes,transcription factors,metabolic activities and tissue-specific expression differences.Resident cell types are characterised by substantial tissue specificity,while tumor-infiltrating cell types are largely shared across cancer types.Finally,by applying the blueprint to melanoma tumors treated with checkpoint immunotherapy and identifying a naive CD4+T-cell phenotype predictive of response to checkpoint immunotherapy,we illustrate how it can serve as a guide to interpret scRNA-seq data.In conclusion,by providing a comprehensive blueprint through an interactive web server,we generate the first panoramic view on the shared complexity of stromal cells in different cancers. | Junbin Qian Siel Olbrecht Bram Boeckx Hanne Vos Damya Laoui Emre Etlioglu Els Wauters Valentina Pomella Sara Verbandt Pieter Busschaert Ayse Bassez Amelie Franken Marlies Vanden Bempt Jieyi Xiong Birgit Weynand Yannick van Herck Asier Antoranz Francesca Maria Bosisio Bernard Thienpont Giuseppe Floris Ignace Vergote Ann Smeets Sabine Tejpar Diether Lambrechts | 2020 | Cell Research2020，30，9： | 11 |
| 3 | Interactions of spatial and luminance information in tile retina of chickens during myopia development显示文摘 | Feldkaemper M Diether S Kleine G | 1999 | Exp Eye Res1999，68，1： | 1 |
| 4 | Misvaluing innova- tion显示文摘 | COHEN L DIETHER K MALLOY C | 2013 | Review of Financial Studies2013，，26： | 1 |
| 5 | Effects of intravitreally and intraperitoneally injected atropine on two types of experimental myopia in chicken显示文摘 | Diether S Schaeffel F Lambrou GN | 2007 | Exp Eye Res2007，84，2： | 1 |
| 6 | Differences of Opinion and the Cross-section of Stock Returns 显示文摘 | DIETHER K B MALLOY C J SCHERBINA A | 2002 | Journal of Finance2002，57，5： | 1 |
| 7 | Local changes in gronth induced by imposed local refractive despite active accommodation显示文摘 | Diether S Schaeffel F | 2004 | Vision Res2004，37，2： | 1 |
| 8 | Short-sale strategies and return predictability 显示文摘 | Diether K B Lee K H Werner I M | 2009 | Review of Financial Studies2009，22，2： | 1 |
| 9 | Differences of opinion and the cross section of stock returns 显示文摘 | Diether K Malloy C Scherbina A | 2002 | Journal of Finance2002，57，5： | 1 |
| 10 | Differences of opinion and the cross section of stock returns显示文摘 | Diether K Malloy C Scherbina A | 2002 | Journal of Finance2002，57，： | 1 |
| 11 | Local changes in eye growth induced by imposed local refractive error despite active accommodation显示文摘 | Diether S Schaeffel F | | 0，，： | 1 |
| 12 | Differences of Opinion and the Cross Section of Stock Returns 显示文摘 | Diether K B C J Malloy and A Scherbina | 2002 | The Journal of Finance2002，57，5： | 1 |
| 13 | Gene prioritization through genomie data fusion显示文摘 | STEIN A DIETHER L SUNIT M et ol | 2006 | Nature Biotechnology2006，24，： | 1 |
| 14 | Local changes in eye growth induced by imposed local refractive error despite active accommodation 显示文摘 | Diether S Schaeffel F | 1997 | Vis Res1997，37，6： | 1 |
| 15 | VEGF pathway genetic variants as biomarkers of treatment outcome with bevacizumab: an analysis of data from the AViTA and AVOREN randomised trials显示文摘 | Diether Lambrechts Bart Claes Paul Delmar Joke Reumers Massimiliano Mazzone Betül T Yesilyurt Roland Devlieger Chris Verslype Sabine Tejpar Hans Wildiers Sanne de Haas Peter Carmeliet Stefan J Scherer Eric Van Cutsem | 2012 | Lancet Oncology2012，，7： | 1 |
| 16 | It is SHO Time! Short-sale Price Tests and Market Quality显示文摘 | DIETHER K B LEE K H WERNER I M | 2009 | The Journal of Finance2009，，64： | 1 |
| 17 | H?ufige Ursachen von Durchfall: Sprue und Lactoseintoleranz显示文摘 | Carsten Jankowiak Diether Ludwig | 2008 | Medizinische Klinik2008，，： | 1 |
| 18 | It is SHO time Short-sale price tests and market quality显示文摘 | DIETHER K B LEE K H WERNER I M | 2009 | The Journal of Finance2009，64，： | 1 |
| 19 | Differences of opinion and the cross section of stock returns显示文摘 | Diether K B | 2002 | Journal of Finance2002，57，5： | 1 |
| 20 | Differences ofop/afion and the cross section of stock returns显示文摘 | Diether K B Malloy C j Scherbina A | 2002 | Journal of Fhaance2002，57，5： | 1 |
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