Dictionary learning for integrative, multimodal and scalable single-cell analysis

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

Published: May 25, 2023

Language: Английский

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A single-cell map of intratumoral changes during anti-PD1 treatment of patients with breast cancer

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(5), P. 820 - 832

Published: May 1, 2021

Language: Английский

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Dysregulation of brain and choroid plexus cell types in severe COVID-19

Nature, Journal Year: 2021, Volume and Issue: 595(7868), P. 565 - 571

Published: June 21, 2021

Language: Английский

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An integrated cell atlas of the lung in health and disease

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(6), P. 1563 - 1577

Published: June 1, 2023

Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations individual the variability present in population. Here we integrated Human Lung Cell Atlas (HLCA), combining 49 respiratory system into single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents consensus re-annotation with matching marker genes, including annotations rare previously undescribed types. Leveraging diversity individuals HLCA, identify gene modules that are associated demographic covariates such as age, sex body mass index, well changing expression along proximal-to-distal axis bronchial tree. Mapping new data to enables rapid annotation interpretation. Using reference for study disease, shared states across multiple lung diseases, SPP1

Language: Английский

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Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease

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

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Neutrophils in COVID-19

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: March 25, 2021

Strong evidence has been accumulated since the beginning of COVID-19 pandemic that neutrophils play an important role in pathophysiology, particularly those with severe disease courses. While originally considered to be a rather homogeneous cell type, recent attention uncovered their fascinating transcriptional and functional diversity as well developmental trajectories. These new findings are better understand many facets neutrophil involvement not only but also other acute or chronic inflammatory diseases, both communicable non-communicable. Here, we highlight observed immune deviation summarize several promising therapeutic attempts precisely target reactivity patients COVID-19.

Language: Английский

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Monocytes and Macrophages in COVID-19

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: July 21, 2021

COVID-19 is a contagious viral disease caused by SARS-CoV-2 that led to an ongoing pandemic with massive global health and socioeconomic consequences. The characterized primarily, but not exclusively, respiratory clinical manifestations ranging from mild common cold symptoms, including cough fever, severe distress multi-organ failure. Macrophages, heterogeneous group of yolk-sac derived, tissue-resident mononuclear phagocytes complex ontogeny present in all mammalian organs, play critical roles developmental, homeostatic host defense processes tissue-dependent plasticity. In case infection, they are responsible for early pathogen recognition, initiation resolution inflammation, as well repair tissue damage. Monocytes, bone-marrow derived blood-resident phagocytes, recruited under pathological conditions such infections the affected defend organism against invading pathogens aid efficient inflammation. Given their pivotal function potential danger posed dysregulated hyperinflammation, understanding monocyte macrophage phenotypes key tackling disease's mechanisms. Here, we outline current knowledge on monocytes macrophages homeostasis summarize concepts findings role COVID-19. While blood patients moderate inflammatory, interferon-stimulated gene (ISG)-driven phenotype, cellular dysfunction epitomized loss HLA-DR expression induction S100 alarmin dominant feature disease. Pulmonary infiltrating inflammatory hyperactivated state resulting detrimental loop pro-inflammatory cytokine release recruitment cytotoxic effector cells thereby exacerbating damage at site infection.

Language: Английский

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The interferon landscape along the respiratory tract impacts the severity of COVID-19

Cell, Journal Year: 2021, Volume and Issue: 184(19), P. 4953 - 4968.e16

Published: Aug. 19, 2021

Severe coronavirus disease 2019 (COVID-19) is characterized by overproduction of immune mediators, but the role interferons (IFNs) type I (IFN-I) or III (IFN-III) families remains debated. We scrutinized production IFNs along respiratory tract COVID-19 patients and found that high levels IFN-III, to a lesser extent IFN-I, characterize upper airways with viral burden reduced risk severity. Production specific not members denotes mild pathology efficiently drives transcription genes protect against severe acute syndrome 2 (SARS-CoV-2). In contrast, compared subjects other infectious noninfectious lung pathologies, are overrepresented in lower exhibit gene pathways associated increased apoptosis decreased proliferation. Our data demonstrate dynamic SARS-CoV-2-infected show play opposing roles at distinct anatomical sites.

Language: Английский

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Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: July 5, 2021

Epidemiological and clinical reports indicate that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate immunopathology underlying COVID-19 severity, we perform cytokine multiplex profiling in patients. We show hypercytokinemia differs from interferon-gamma-driven storm macrophage activation syndrome, is pronounced critical versus mild-moderate COVID-19. Systems modelling levels paired with deep-immune shows classical monocytes drive this hyper-inflammatory phenotype a reduction T-lymphocytes correlates disease CD8+ cells being disproportionately affected. Antigen presenting machinery expression also reduced disease. Furthermore, report neutrophils contribute to severity local tissue damage by amplification formation neutrophil extracellular traps. Together our findings suggest myeloid-driven immunopathology, which hyperactivated ineffective adaptive system act as mediators severity.

Language: Английский

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Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19

Cell, Journal Year: 2021, Volume and Issue: 184(7), P. 1836 - 1857.e22

Published: Feb. 10, 2021

Language: Английский

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