Biology subjects

Driscoll, J.

Publications and source records attributed to Driscoll, J..

3 recordsLinked to original sources

bioRxiv2025

Spatial Heterogeneity of Macrophages in the Human Lung

RationaleTranscriptionally-defined populations of interstitial macrophages (IMs) and airspace macrophages (AMs) have recently been identified in the human lung. However, the anatomic locations occupied by these populations (i.e. alveoli, pleura, airways, or arteries) have not been fully defined. ObjectivesTo determine the distribution of transcriptionally-defined human macrophages in the major anatomical lung structures and to identify alterations in their distribution and programming induced by cigarette smoking. MethodsSingle-cell RNA sequencing was performed on lung tissue from eight human donors without pulmonary disease (four smokers and four nonsmokers). Microdissection was used to isolate distinct pulmonary anatomical structures from each lung: alveoli, pleura, airways, and arteries. Transcriptional profiles of subpopulations of interstitial macrophages (IMs) and alveolar macrophages (AMs) were analyzed based on their anatomical structure of origin and smoking status. Measurements and Main ResultsFive major IM and five AM subpopulations in human lungs are identified. We demonstrate significant differences in the accumulation patterns of each macrophage subset within anatomical structures, though each subset was detected in each. Immunofluorescent microscopy confirmed anatomical structure-specific accumulation patterns of IMs. ConclusionsIn this study, we highlight key differences in the accumulation of lung macrophage subpopulations in anatomical structures but find programming within macrophage subpopulations is largely conserved, regardless of structure of origin or smoking status. We also detect populations of inflammatory AMs and IMs which accumulate within the airways, but not the alveolar parenchyma, of human cigarette smokers. We introduce a novel three-tiered hierarchy nomenclature to distinguish transcriptionally defined human lung IM subsets as 1{degrees}) Monocyte-like vs Antigen Presenting, 2{degrees}) Quiescent vs Inflammatory, and 3{degrees}) FOLR2high vs FOLR2low. This study is the first to report the fractional accumulation of human lung macrophage subsets by lung anatomical structure. SummaryLung anatomical structure-specific single cell RNA sequencing is introduced to identify and determine the local composition of human lung leukocytes, including 5 populations of human interstitial macrophages.

immunology↗

bioRxiv2023

Climate benefits of seaweed farming: estimating regional carbon emission and sequestration pathways

Seaweed farming is widely promoted as an approach to mitigating climate change despite limited data on carbon removal pathways and uncertainty around benefits and risks at operational scales. We explored the feasibility of seaweed farms to contribute to atmospheric CO2 reduction in coastal British Columbia, Canada, a region identified as highly suitable for seaweed farming. Using a place-based, quantitative model, we examined five scenarios spanning a range of industry development. Our intermediate growth scenario sequestered or avoided 0.20 Tg CO2e / year, while our most ambitious scenario (with more cultivation and higher production rates) yielded a reduction of 8.2 Tg CO2e /year, equivalent to 0.3% and 13% of annual greenhouse gas emissions in BC, respectively. Across all scenarios, climate benefits depended on seaweed-based products replacing more emissions-intensive products. Marine sequestration was relatively inefficient in comparison, although production rates and avoided emissions are key uncertainties prioritized for future research. Our results show how seaweed farming could contribute to Canadas climate goals, and our model illustrates how farmers, regulators, and researchers could accurately quantify the climate benefits of seaweed farming in local contexts.

ecology↗

bioRxiv2023

Tissue-engineered models of lung cancer premalignancy

Lung cancer is the leading global cause of cancer-related deaths. Although smoking cessation is the best preventive action, nearly 50% of all lung cancer diagnoses occur in people who have already quit smoking. Research into treatment options for these high-risk patients has been constrained to rodent models of chemical carcinogenesis, which are time-consuming, expensive, and require large numbers of animals. Here we show that embedding precision-cut lung slices within an engineered hydrogel and exposing this tissue to a carcinogen from cigarette smoke creates an in vitro model of lung cancer premalignancy. Hydrogel formulations were selected to promote early lung cancer cellular phenotypes and extend PCLS viability up to six weeks. In this study, hydrogel-embedded lung slices were exposed to the cigarette smoke derived carcinogen vinyl carbamate, which induces adenocarcinoma in mice. At six weeks, analysis of proliferation, gene expression, histology, tissue stiffness, and cellular content revealed that vinyl carbamate induced the formation of premalignant lesions with a mixed adenoma/squamous phenotype. Two putative chemoprevention agents were able to freely diffuse through the hydrogel and induce tissue-level changes. The design parameters selected using murine tissue were validated with hydrogel-embedded human PCLS and results showed increased proliferation and premalignant lesion gene expression patterns. This tissue-engineered model of human lung cancer premalignancy is the starting point for more sophisticated ex vivo models and a foundation for the study of carcinogenesis and chemoprevention strategies.

bioengineering↗