Biomarkers of aging

Science China Life Sciences, Год журнала: 2023, Номер 66(5), С. 893 - 1066

Опубликована: Апрель 11, 2023

Язык: Английский

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A single-cell transcriptomic landscape of the lungs of patients with COVID-19

Nature Cell Biology, Год журнала: 2021, Номер 23(12), С. 1314 - 1328

Опубликована: Дек. 1, 2021

Язык: Английский

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Human alveolar type 2 epithelium transdifferentiates into metaplastic KRT5+ basal cells

Nature Cell Biology, Год журнала: 2021, Номер 24(1), С. 10 - 23

Опубликована: Дек. 30, 2021

Язык: Английский

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A single-cell atlas of mouse lung development

Development, Год журнала: 2021, Номер 148(24)

Опубликована: Дек. 15, 2021

ABSTRACT Lung organogenesis requires precise timing and coordination to effect spatial organization function of the parenchymal cells. To provide a systematic broad-based view mechanisms governing dynamic alterations in cells over crucial periods development, we performed single-cell RNA-sequencing time-series yielding 102,571 epithelial, endothelial mesenchymal across nine time points from embryonic day 12 postnatal 14 mice. Combining computational fate-likelihood prediction with RNA situ hybridization immunofluorescence, explore lineage relationships during saccular alveolar stage transition. The utility this publicly searchable atlas resource (www.sucrelab.org/lungcells) is exemplified by discoveries complexity type 1 pneumocyte characterization Wnt expression patterns stages – wherein major expansion gas-exchange surface occurs. We an integrated cellular dynamics cell populations lung organogenesis.

Язык: Английский

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Ferroptotic stress promotes the accumulation of pro-inflammatory proximal tubular cells in maladaptive renal repair

eLife, Год журнала: 2021, Номер 10

Опубликована: Июль 19, 2021

Overwhelming lipid peroxidation induces ferroptotic stress and ferroptosis, a non-apoptotic form of regulated cell death that has been implicated in maladaptive renal repair mice humans. Using single-cell transcriptomic mouse genetic approaches, we show proximal tubular (PT) cells develop molecularly distinct, pro-inflammatory state following injury. While these inflammatory PT transiently appear after mild injury return to their original without inducing fibrosis, severe they accumulate contribute persistent inflammation. This transient significantly downregulates glutathione metabolism genes, making the vulnerable stress. Genetic induction high leads accumulation cells, enhancing inflammation fibrosis. Our study broadens roles from being trigger include promotion proinflammatory underlie repair.

Язык: Английский

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Lung Adenocarcinoma Tumor Origin: A Guide for Personalized Medicine

Cancers, Год журнала: 2022, Номер 14(7), С. 1759 - 1759

Опубликована: Март 30, 2022

Lung adenocarcinoma, the major form of lung cancer, is deadliest cancer worldwide, due to its late diagnosis and high heterogeneity. Indeed, adenocarcinoma exhibits pronounced inter- intra-tumor heterogeneity cofounding precision medicine. Tumor a clinical challenge driving tumor progression drug resistance. Several key pieces evidence demonstrated that results from transformation progenitor cells accumulate genetic abnormalities. Thus, better understanding cell origin represents an opportunity unveil new therapeutic alternatives stratify patient tumors. While remarkably quiescent during homeostasis, it presents extensive ability respond injury regenerate lost or damaged cells. As constantly exposed potential insult, regenerative assured by several stem These can be induced proliferate in response as well differentiate into multiple types. A how alterations perturbed microenvironments impact progenitor-mediated tumorigenesis treatment utmost importance develop opportunities.

Язык: Английский

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Regeneration or Repair? The Role of Alveolar Epithelial Cells in the Pathogenesis of Idiopathic Pulmonary Fibrosis (IPF)

Cells, Год журнала: 2022, Номер 11(13), С. 2095 - 2095

Опубликована: Июнь 30, 2022

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease (ILD) with unknown etiology in which gradual fibrotic scarring of the lungs leads to usual pneumonia (UIP) and, ultimately, death. IPF affects three million people worldwide, and only currently available treatments include antifibrotic drugs nintedanib pirfenidone, effectively reduce progression are, unfortunately, not effective curing disease. In recent years, paradigm pathogenesis has shifted from fibroblast-driven an epithelium-driven disease, wherein, upon recurrent microinjuries, dysfunctional alveolar type II epithelial cells (ATII) are unable sustain physiological regeneration but also promote aberrant epithelial-mesenchymal crosstalk. This creates drift towards rather than regeneration. context this review article, we discuss most relevant mechanisms involved specific focus on role ATII promoting progression. particular, summarize main causes cell dysfunction, such as aging, environmental factors, genetic determinants. Next, describe known by drawing parallel between embryonic development pathways ATII-driven re-epithelization after injury. Finally, interventional clinical trials performed last 20 years aim underlining urgency developing new therapies against that aimed at reducing hampering ECM deposition boost processes

Язык: Английский

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Human organoids: New strategies and methods for analyzing human development and disease

Cell, Год журнала: 2022, Номер 185(15), С. 2756 - 2769

Опубликована: Июль 1, 2022

For decades, insight into fundamental principles of human biology and disease has been obtained primarily by experiments in animal models. While this allowed researchers to understand many biological processes great detail, some developmental mechanisms have proven difficult study due inherent species differences. The advent organoid technology more than 10 years ago established laboratory-grown organ tissues as an additional model system recapitulate human-specific aspects biology. use 3D organoids, well other advances single-cell technologies, revealed unprecedented insights mechanisms, especially those that distinguish humans from species. This review highlights novel with a focus on how generated better understanding development disease.

Язык: Английский

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SARS-CoV-2 infection produces chronic pulmonary epithelial and immune cell dysfunction with fibrosis in mice

Science Translational Medicine, Год журнала: 2022, Номер 14(664)

Опубликована: Июль 7, 2022

A subset of individuals who recover from coronavirus disease 2019 (COVID-19) develop post-acute sequelae severe acute respiratory syndrome 2 (SARS-CoV-2) (PASC), but the mechanistic basis PASC-associated lung abnormalities suffers a lack longitudinal tissue samples. The mouse-adapted SARS-CoV-2 strain MA10 produces an distress in mice similar to humans. To investigate PASC pathogenesis, studies MA10-infected were extended clinical recovery phases. At 15 120 days after virus clearance, pulmonary histologic findings included subpleural lesions composed collagen, proliferative fibroblasts, and chronic inflammation, including tertiary lymphoid structures. Longitudinal spatial transcriptional profiling identified global reparative fibrotic pathways dysregulated diseased regions, human COVID-19. Populations alveolar intermediate cells, coupled with focal up-regulation profibrotic markers, persistently regions. Early intervention antiviral EIDD-2801 reduced disease, early antifibrotic agent (nintedanib) modified severity. This murine model provides opportunities identify associated persistent test countermeasures ameliorate PASC.

Язык: Английский

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Macrophage phenotypes and functions: resolving inflammation and restoring homeostasis

Trends in Immunology, Год журнала: 2023, Номер 44(12), С. 986 - 998

Опубликована: Ноя. 6, 2023

Язык: Английский

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