Effect of invasive mechanical ventilation on the diversity of the pulmonary microbiota DOI Creative Commons
Chang Liu, Kang Wu,

Tianyu Sun

et al.

Critical Care, Journal Year: 2022, Volume and Issue: 26(1)

Published: Aug. 22, 2022

Abstract Pulmonary microbial diversity may be influenced by biotic or abiotic conditions (e.g., disease, smoking, invasive mechanical ventilation (MV), etc.). Specially, MV trigger structural and physiological changes in both tissue microbiota of lung, due to gastric oral microaspiration, altered body posture, high O 2 inhalation-induced toxicity hypoxemic patients, impaired airway clearance ventilator-induced lung injury (VILI), which turn reduce the pulmonary ultimately lead poor prognosis. Furthermore, (local) concentration can affecting local immune microenvironment lung. In conclusion, systematic literature studies have found that reduces diversity, future rational regulation existing novel clinical tools probiotics, drugs) improve prognosis treatment more effective diseases with precision.

Language: Английский

Vascular endothelial cell development and diversity DOI Open Access
Emily Trimm, Kristy Red‐Horse

Nature Reviews Cardiology, Journal Year: 2022, Volume and Issue: 20(3), P. 197 - 210

Published: Oct. 5, 2022

Language: Английский

Citations

266
Mitochondrial integrated stress response controls lung epithelial cell fate DOI Creative Commons
SeungHye Han, Minho Lee, Youngjin Shin

et al.

Nature, Journal Year: 2023, Volume and Issue: 620(7975), P. 890 - 897

Published: Aug. 9, 2023

Abstract Alveolar epithelial type 1 (AT1) cells are necessary to transfer oxygen and carbon dioxide between the blood air. 2 (AT2) serve as a partially committed stem cell population, producing AT1 during postnatal alveolar development repair after influenza A SARS-CoV-2 pneumonia 1–6 . Little is known about metabolic regulation of fate lung cells. Here we report that deleting mitochondrial electron transport chain complex I subunit Ndufs2 in mouse gestation led death development. Affected mice displayed hypertrophic with AT2 features, transitional Mammalian I, comprising 45 subunits, regenerates NAD + pumps protons. Conditional expression yeast NADH dehydrogenase (NDI1) protein without proton pumping 7,8 was sufficient correct abnormal avert lethality. Single-cell RNA sequencing revealed enrichment integrated stress response (ISR) genes Administering an ISR inhibitor 9,10 or precursor reduced gene signatures rescued lethality absence function. Notably, epithelial-specific loss II Sdhd , which maintains regeneration, did not trigger high activation These findings highlight unanticipated requirement for I-dependent regeneration directing by preventing pathological induction.

Language: Английский

Citations

65
A topographic atlas defines developmental origins of cell heterogeneity in the human embryonic lung DOI Creative Commons
Alexandros Sountoulidis, Sergio Marco Salas, Emelie Braun

et al.

Nature Cell Biology, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 16, 2023

Abstract The lung contains numerous specialized cell types with distinct roles in tissue function and integrity. To clarify the origins mechanisms generating heterogeneity, we created a comprehensive topographic atlas of early human development. Here report 83 states several spatially resolved developmental trajectories predict interactions within defined niches. We integrated single-cell RNA sequencing transcriptomics into web-based, open platform for interactive exploration. show gene expression programmes, accompanying sequential events differentiation maturation secretory neuroendocrine proximal epithelium. define origin airway fibroblasts associated smooth muscle bronchovascular bundles describe trajectory Schwann progenitors to intrinsic parasympathetic neurons controlling bronchoconstriction. Our provides rich resource further research reference defining deviations from homeostatic repair leading pulmonary diseases.

Language: Английский

Citations

45
Deciphering endothelial heterogeneity in health and disease at single-cell resolution: progress and perspectives DOI
Lisa M. Becker, Shiau-Haln Chen, Julie Rodor

et al.

Cardiovascular Research, Journal Year: 2022, Volume and Issue: 119(1), P. 6 - 27

Published: Feb. 16, 2022

Endothelial cells (ECs) constitute the inner lining of vascular beds in mammals and are crucial for homeostatic regulation blood vessel physiology, but also play a key role pathogenesis many diseases, thereby representing realistic therapeutic targets. However, it has become evident that ECs heterogeneous, encompassing several subtypes with distinct functions, which makes EC targeting modulation diseases challenging. The rise new single-cell era led to an emergence studies aimed at interrogating transcriptome diversity along tree, revolutionized our understanding heterogeneity from both physiological pathophysiological context. Here, we discuss recent landmark teasing apart heterogeneous nature ECs. We cover driving (epi)genetic, transcriptomic, metabolic forces underlying health disease, as well current strategies used combat disease-enriched phenotypes, propose transcend largely descriptive towards prioritization functional validation therapeutically targetable drivers diversity. Lastly, provide overview most advances hurdles single OMICs.

Language: Английский

Citations

42
Common human genetic variants of APOE impact murine COVID-19 mortality DOI Open Access
Benjamin N. Ostendorf, Mira A. Patel, Jana Bilanovic

et al.

Nature, Journal Year: 2022, Volume and Issue: 611(7935), P. 346 - 351

Published: Sept. 21, 2022

Language: Английский

Citations

42
Pulmonary inflammation and fibroblast immunoregulation: from bench to bedside DOI Creative Commons
Mohamed A. Ghonim, David F. Boyd,

Tim Flerlage

et al.

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(17)

Published: Aug. 31, 2023

In recent years, there has been an explosion of interest in how fibroblasts initiate, sustain, and resolve inflammation across disease states. Fibroblasts contain heterogeneous subsets with diverse functionality. The phenotypes these populations vary depending on their spatial distribution within the tissue immunopathologic cues contributing to progression. addition roles structurally supporting organs remodeling tissue, mediate critical interactions immune cells. These have important implications for defining mechanisms identifying potential therapeutic targets. respiratory tract, particular, determine severity outcome numerous acute chronic lung diseases, including asthma, obstructive pulmonary disease, distress syndrome, idiopathic fibrosis. Here, we review studies spatiotemporal identity lung-derived by which regulate responses insult exposures highlight past, current, future targets relevance fibroblast biology context human diseases. This perspective highlights importance fibroblast-immune crosstalk paves way approaches benefit patients disorders.

Language: Английский

Citations

26
Mechanistic Understanding of Lung Inflammation: Recent Advances and Emerging Techniques DOI Creative Commons
Chrysi Keskinidou, Alice G. Vassiliou, Ioanna Dimopoulou

et al.

Journal of Inflammation Research, Journal Year: 2022, Volume and Issue: Volume 15, P. 3501 - 3546

Published: June 1, 2022

Abstract: Acute respiratory distress syndrome (ARDS) is a life-threatening lung injury characterized by an acute inflammatory response in the parenchyma. Hence, it considered as most appropriate clinical to study pathogenic mechanisms of inflammation. ARDS associated with increased morbidity and mortality intensive care unit (ICU), while no effective pharmacological treatment exists. It very important therefore fully characterize underlying pathobiology related mechanisms, order develop novel therapeutic approaches. In vivo vitro models are pre-clinical tools biological medical research mechanistic pathological understanding majority diseases. this review, we will present data from selected experimental injury/acute inflammation, which have been based on disorders that can lead development processes humans, including ventilation-induced (VILI), sepsis, ischemia/reperfusion, smoke, acid aspiration, radiation, transfusion-related (TRALI), influenza, Streptococcus ( S .) pneumoniae coronaviruses infection. Data corresponding conditions also be presented. The inflammation covered oxidative stress, neutrophil extracellular traps, mitogen-activated protein kinase (MAPK) pathways, surfactant, water ion channels. Finally, brief overview emerging techniques field omics applied research, encompassing genomics, transcriptomics, proteomics, metabolomics, may recognize factors help stratify ICU patients at risk, predict their prognosis, possibly, serve more specific targets. Keywords: syndrome, biomarkers,

Language: Английский

Citations

32
Complex roles of TGF-β signaling pathways in lung development and bronchopulmonary dysplasia DOI
Rebecca J Calthorpe,

Caroline Poulter,

Alan R Smyth

et al.

AJP Lung Cellular and Molecular Physiology, Journal Year: 2023, Volume and Issue: 324(3), P. L285 - L296

Published: Jan. 10, 2023

As survival of extremely preterm infants continues to improve, there is also an associated increase in bronchopulmonary dysplasia (BPD), one the most significant complications birth. BPD development multifactorial resulting from exposure multiple antenatal and postnatal stressors. has both short-term health implications long-term sequelae including increased respiratory, cardiovascular, neurological morbidity. Transforming growth factor β (TGF-β) important signaling pathway lung development, organ injury, fibrosis implicated BPD. This review provides a detailed account on role TGF-β effect known risk factors for pathway, how medications currently use or under prevention treatment BPD, affect signaling.

Language: Английский

Citations

23
LY6E is a pan-coronavirus restriction factor in the respiratory tract DOI
Katrina B. Mar, Alexandra I. Wells, Marley C. Caballero Van Dyke

et al.

Nature Microbiology, Journal Year: 2023, Volume and Issue: 8(8), P. 1587 - 1599

Published: July 13, 2023

Language: Английский

Citations

20
pIGLET : Safe harbor landing sites for reproducible and efficient transgenesis in zebrafish DOI Creative Commons
Robert L. Lalonde, Harrison H. Wells, Cassie L. Kemmler

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(23)

Published: June 5, 2024

Standard zebrafish transgenesis involves random transgene integration with resource-intensive screening. While phiC31 integrase–based attP / attB recombination has streamlined in mice and Drosophila , validated -based landing sites for universal applications are lacking zebrafish. Here, we developed Integrase Genomic Loci Engineered Transgenesis ( pIGLET ) as approach, two pIGLET14a pIGLET24b from well-validated Tol2 transgenes. Both facilitate diverse including reporters Cre/ loxP The consistently yield 25 to 50% germline transmission, substantially reducing the resources needed transgenic line generation. into these enables reproducible expression patterns F0 embryos enhancer discovery testing of gene regulatory variants. Together, our new streamline targeted, a robust platform various while minimizing workload generating lines.

Language: Английский

Citations

7