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

Nature, Journal Year: 2021, Volume and Issue: 595(7865), P. 107 - 113

Published: April 29, 2021

Language: Английский

---

SARS-CoV-2 pathogenesis

Nature Reviews Microbiology, Journal Year: 2022, Volume and Issue: 20(5), P. 270 - 284

Published: March 30, 2022

Language: Английский

---

The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity

The Lancet Respiratory Medicine, Journal Year: 2021, Volume and Issue: 9(6), P. 622 - 642

Published: May 7, 2021

The zoonotic SARS-CoV-2 virus that causes COVID-19 continues to spread worldwide, with devastating consequences. While the medical community has gained insight into epidemiology of COVID-19, important questions remain about clinical complexities and underlying mechanisms disease phenotypes. Severe most commonly involves respiratory manifestations, although other systems are also affected, acute is often followed by protracted complications. Such complex manifestations suggest dysregulates host response, triggering wide-ranging immuno-inflammatory, thrombotic, parenchymal derangements. We review intricacies pathophysiology, its various phenotypes, anti-SARS-CoV-2 response at humoral cellular levels. Some similarities exist between failure origins, but evidence for many distinctive mechanistic features indicates constitutes a new entity, emerging data suggesting involvement an endotheliopathy-centred pathophysiology. Further research, combining basic studies, needed advance understanding pathophysiological characterise immuno-inflammatory derangements across range phenotypes enable optimum care patients COVID-19.

Language: Английский

---

Inflammasome activation in infected macrophages drives COVID-19 pathology

Nature, Journal Year: 2022, Volume and Issue: 606(7914), P. 585 - 593

Published: April 28, 2022

Language: Английский

---

SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis

Cell, Journal Year: 2021, Volume and Issue: 184(26), P. 6243 - 6261.e27

Published: Nov. 27, 2021

Language: Английский

---

Mapping single-cell data to reference atlases by transfer learning

Nature Biotechnology, Journal Year: 2021, Volume and Issue: 40(1), P. 121 - 130

Published: Aug. 30, 2021

Abstract Large single-cell atlases are now routinely generated to serve as references for analysis of smaller-scale studies. Yet learning from reference data is complicated by batch effects between datasets, limited availability computational resources and sharing restrictions on raw data. Here we introduce a deep strategy mapping query datasets top called architectural surgery (scArches). scArches uses transfer parameter optimization enable efficient, decentralized, iterative building contextualization new with existing without Using examples mouse brain, pancreas, immune whole-organism atlases, show that preserves biological state information while removing effects, despite using four orders magnitude fewer parameters than de novo integration. generalizes multimodal mapping, allowing imputation missing modalities. Finally, retains coronavirus disease 2019 (COVID-19) variation when healthy reference, enabling the discovery disease-specific cell states. will facilitate collaborative projects construction, updating, efficient use atlases.

Language: Английский

---

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

---

SARS-CoV-2 spike protein induces inflammation via TLR2-dependent activation of the NF-κB pathway

eLife, Journal Year: 2021, Volume and Issue: 10

Published: Dec. 6, 2021

The pathogenesis of COVID-19 is associated with a hyperinflammatory response; however, the precise mechanism SARS-CoV-2-induced inflammation poorly understood. Here, we investigated direct inflammatory functions major structural proteins SARS-CoV-2. We observed that spike (S) protein potently induced cytokines and chemokines, including IL-6, IL-1β, TNFα, CXCL1, CXCL2, CCL2, but not IFNs in human mouse macrophages. No such response was to membrane (M), envelope (E), nucleocapsid (N) proteins. When stimulated extracellular S protein, lung epithelial cells also produced chemokines. Interestingly, expressing intracellularly were non-inflammatory, elicited an macrophages when co-cultured. Biochemical studies revealed triggers via activation NF-κB pathway MyD88-dependent manner. Further, abrogated Tlr2-deficient Consistently, administration protein-induced TNF-α, IL-1β wild-type, mice. Notably, upon recognition TLR2 dimerizes TLR1 or TLR6 activate pathway. Taken together, these data reveal for cytokine storm during SARS-CoV-2 infection suggest could be potential therapeutic target COVID-19.

Language: Английский

---

Macrophages in health and disease

Cell, Journal Year: 2022, Volume and Issue: 185(23), P. 4259 - 4279

Published: Nov. 1, 2022

Language: Английский

---

Biology of lung macrophages in health and disease

Immunity, Journal Year: 2022, Volume and Issue: 55(9), P. 1564 - 1580

Published: Sept. 1, 2022

Language: Английский

---