A spatially resolved atlas of the human lung characterizes a gland-associated immune niche DOI Creative Commons
Elo Madissoon, Amanda J. Oliver, Vitalii Kleshchevnikov

et al.

Nature Genetics, Journal Year: 2022, Volume and Issue: 55(1), P. 66 - 77

Published: Dec. 21, 2022

Abstract Single-cell transcriptomics has allowed unprecedented resolution of cell types/states in the human lung, but their spatial context is less well defined. To (re)define tissue architecture lung and airways, we profiled five proximal-to-distal locations healthy lungs depth using multi-omic single cell/nuclei (queryable at lungcellatlas.org ). Using computational data integration analysis, extend beyond suspension paradigm discover macro micro-anatomical compartments including previously unannotated types epithelial, vascular, stromal nerve bundle micro-environments. We identify implicate peribronchial fibroblasts disease. Importantly, validate a survival niche for IgA plasma cells airway submucosal glands (SMG). show that gland epithelial recruit B cells, promote longevity antibody secretion locally through expression CCL28, APRIL IL-6. This new ‘gland-associated immune niche’ implications respiratory health.

Language: Английский

Dictionary learning for integrative, multimodal and scalable single-cell analysis DOI Open Access
Yuhan Hao, Tim Stuart, Madeline H. Kowalski

et al.

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 42(2), P. 293 - 304

Published: May 25, 2023

Language: Английский

Citations

1410
Multiple early factors anticipate post-acute COVID-19 sequelae DOI Creative Commons
Yapeng Su, Dan Yuan, Daniel Chen

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(5), P. 881 - 895.e20

Published: Jan. 25, 2022

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation 309 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data patient-reported symptoms. resolved four PASC-anticipating at the time diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, specific auto-antibodies. In gastrointestinal PASC, SARS-CoV-2-specific CMV-specific CD8+ T cells exhibited unique dynamics during recovery COVID-19. Analysis symptom-associated immunological signatures revealed coordinated immunity polarization into endotypes, exhibiting divergent acute severity PASC. find that between diminish over time, leading distinct convalescent immune states. Detectability most emphasizes importance early disease measurements understanding emergent chronic conditions suggests treatment strategies.

Language: Английский

Citations

918
Best practices for single-cell analysis across modalities DOI Open Access
Lukas Heumos, Anna C. Schaar, Christopher Lance

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 24(8), P. 550 - 572

Published: March 31, 2023

Language: Английский

Citations

527
The technological landscape and applications of single-cell multi-omics DOI Open Access
Alev Baysoy, Zhiliang Bai, Rahul Satija

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 24(10), P. 695 - 713

Published: June 6, 2023

Language: Английский

Citations

461
Systems vaccinology of the BNT162b2 mRNA vaccine in humans DOI Open Access
Prabhu S. Arunachalam, Madeleine Scott, Thomas Hagan

et al.

Nature, Journal Year: 2021, Volume and Issue: 596(7872), P. 410 - 416

Published: July 12, 2021

Language: Английский

Citations

459
Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) DOI Creative Commons
Andrea Cossarizza, Hyun‐Dong Chang, Andreas Radbruch

et al.

European Journal of Immunology, Journal Year: 2021, Volume and Issue: 51(12), P. 2708 - 3145

Published: Dec. 1, 2021

Abstract The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes functional assays all major human murine immune cell subsets. Notably, contain helpful tables highlighting differences between cells. Another useful feature this is analysis clinical samples with examples applications in context autoimmune diseases, cancers as well acute chronic infectious diseases. Furthermore, there are detailing tips, tricks pitfalls avoid. All written peer‐reviewed by leading experts immunologists, making an essential state‐of‐the‐art handbook for basic researchers.

Language: Английский

Citations

323
The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19 DOI
Christoph Schultheiß, Edith Willscher, Lisa Paschold

et al.

Cell Reports Medicine, Journal Year: 2022, Volume and Issue: 3(6), P. 100663 - 100663

Published: June 1, 2022

Language: Английский

Citations

320
Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease DOI Creative Commons
Laura Bergamaschi, Federica Mescia, Lorinda Turner

et al.

Immunity, Journal Year: 2021, Volume and Issue: 54(6), P. 1257 - 1275.e8

Published: May 16, 2021

The kinetics of the immune changes in COVID-19 across severity groups have not been rigorously assessed. Using immunophenotyping, RNA sequencing, and serum cytokine analysis, we analyzed serial samples from 207 SARS-CoV2-infected individuals with a range disease severities over 12 weeks symptom onset. An early robust bystander CD8+ T cell response, without systemic inflammation, characterized asymptomatic or mild disease. Hospitalized had delayed responses inflammation that was already evident near onset, indicating immunopathology may be inevitable some individuals. Viral load did correlate this pathological response but subsequent severity. Immune recovery is complex, profound persistent cellular abnormalities severe correlating altered inflammatory responses, signatures associated increased oxidative phosphorylation replacing those driven by cytokines tumor necrosis factor (TNF) interleukin (IL)-6. These late immunometabolic defects clinical implications.

Language: Английский

Citations

311
Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19 DOI Creative Commons
Carly G.K. Ziegler, Vincent N. Miao, Anna H. Owings

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(18), P. 4713 - 4733.e22

Published: July 23, 2021

SARS-CoV-2 infection can cause severe respiratory COVID-19. However, many individuals present with isolated upper symptoms, suggesting potential to constrain viral pathology the nasopharynx. Which cells primarily targets and how influences epithelium remains incompletely understood. We performed scRNA-seq on nasopharyngeal swabs from 58 healthy COVID-19 participants. During COVID-19, we observe expansion of secretory, loss ciliated, epithelial cell repopulation via deuterosomal expansion. In mild moderate express anti-viral/interferon-responsive genes, while in have muted anti-viral responses despite equivalent loads. RNA

Language: Английский

Citations

283
A blood atlas of COVID-19 defines hallmarks of disease severity and specificity DOI Creative Commons
David Ahern, Zhichao Ai, Mark Ainsworth

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(5), P. 916 - 938.e58

Published: Jan. 21, 2022

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying severity in an integrated comparison influenza sepsis versus healthy volunteers. identify signatures correlates host response. Hallmarks disease involved cells, their inflammatory mediators networks, including progenitor cells myeloid lymphocyte subsets, features the repertoire, acute phase response, metabolism, coagulation. Persisting activation involving AP-1/p38MAPK was feature COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive outcome. Systems-based integrative analyses tensor matrix decomposition all modalities revealed groupings linked specificity compared to sepsis. Our approach will support future drug development, trial design, personalized medicine approaches

Language: Английский

Citations

267