Microanatomy of the Human Atherosclerotic Plaque by Single-Cell Transcriptomics

Rationale:Atherosclerotic lesions are known for their cellular heterogeneity, yet the molecular complexity within the cells of human plaques has not been fully assessed.Objective:Using single-cell transcriptomics and chromatin accessibility, we gained a better understanding of the pathophysiology underlying human atherosclerosis.Methods and Results:We performed single-cell RNA and single-cell ATAC sequencing on human carotid atherosclerotic plaques to define the cells at play and determine their transcriptomic and epigenomic characteristics. We identified 14 distinct cell populations including endothelial cells, smooth muscle cells, mast cells, B cells, myeloid cells, and T cells and identified multiple cellular activation states and suggested cellular interconversions. Within the endothelial cell population, we defined subsets with angiogenic capacity plus clear signs of endothelial to mesenchymal transition. CD4(+) and CD8(+) T cells showed activation-based subclasses, each with a gradual decline from a cytotoxic to a more quiescent phenotype. Myeloid cells included 2 populations of proinflammatory macrophages showing IL (interleukin) 1B or TNF (tumor necrosis factor) expression as well as a foam cell-like population expressing TREM2 (triggering receptor expressed on myeloid cells 2) and displaying a fibrosis-promoting phenotype. ATACseq data identified specific transcription factors associated with the myeloid subpopulation and T cell cytokine profiles underlying mutual activation between both cell types. Finally, cardiovascular disease susceptibility genes identified using public genome-wide association studies data were particularly enriched in lesional macrophages, endothelial, and smooth muscle cells.Conclusions:This study provides a transcriptome-based cellular landscape of human atherosclerotic plaques and highlights cellular plasticity and intercellular communication at the site of disease. This detailed definition of cell communities at play in atherosclerosis will facilitate cell-based mapping of novel interventional targets with direct functional relevance for the treatment of human disease

Building the Policy Ecosystem in Europe for Cultivation and Use of Perennial Biomass Crops

Perennial biomass crops (PBCs) can potentially contribute to all ten Common Agricultural Policy (2023-27) objectives and up to eleven of the seventeen UN Sustainable Development Goals. This paper discusses interlinked issues that must be considered in the expansion of PBC production: i) available land; ii) yield potential; iii) integration into farming systems; iv) research and development requirements; v) utilisation options; and vi) market systems and the socio-economic environment. The challenge to create development pathways that are acceptable for all actors, relies on measurement, reporting and verification of greenhouse gas emissions reduction in combination with other environmental, economic and social aspects. This paper makes the following policy recommendations to enable greater PBC deployment: 1) incentivise farmers and land managers through specific policy measures, including carbon pricing, to allocate their less productive and less profitable land for uses which deliver demonstrable greenhouse gas reductions; 2) enable greenhouse gas mitigation markets to develop and offer secure contracts for commercial developers of verifiable low carbon bioenergy and bio-products; 3) support innovation in biomass utilisation value chains; and 4) continue long-term, strategic research and development and education for positive environmental, economic and social sustainability impacts. © 2023 ETA-Florence Renewable Energies

Microanatomy of the Human Atherosclerotic Plaque by Single-Cell Transcriptomics

RATIONALE: Atherosclerotic lesions are known for their cellular heterogeneity, yet the molecular complexity within the cells of human plaques has not been fully assessed. OBJECTIVE: Using single-cell transcriptomics and chromatin accessibility, we gained a better understanding of the pathophysiology underlying human atherosclerosis. METHODS AND RESULTS: We performed single-cell RNA and single-cell ATAC sequencing on human carotid atherosclerotic plaques to define the cells at play and determine their transcriptomic and epigenomic characteristics. We identified 14 distinct cell populations including endothelial cells, smooth muscle cells, mast cells, B cells, myeloid cells, and T cells and identified multiple cellular activation states and suggested cellular interconversions. Within the endothelial cell population, we defined subsets with angiogenic capacity plus clear signs of endothelial to mesenchymal transition. CD4+ and CD8+ T cells showed activation-based subclasses, each with a gradual decline from a cytotoxic to a more quiescent phenotype. Myeloid cells included 2 populations of proinflammatory macrophages showing IL (interleukin) 1B or TNF (tumor necrosis factor) expression as well as a foam cell-like population expressing TREM2 (triggering receptor expressed on myeloid cells 2) and displaying a fibrosis-promoting phenotype. ATACseq data identified specific transcription factors associated with the myeloid subpopulation and T cell cytokine profiles underlying mutual activation between both cell types. Finally, cardiovascular disease susceptibility genes identified using public genome-wide association studies data were particularly enriched in lesional macrophages, endothelial, and smooth muscle cells. CONCLUSIONS: This study provides a transcriptome-based cellular landscape of human atherosclerotic plaques and highlights cellular plasticity and intercellular communication at the site of disease. This detailed definition of cell communities at play in atherosclerosis will facilitate cell-based mapping of novel interventional targets with direct functional relevance for the treatment of human disease

Microanatomy of the Human Atherosclerotic Plaque by Single-Cell Transcriptomics

These are the single-cell RNAseq data from the Athero-Express Biobank Study as used after quality control in the paper referenced below; below the abstract. Rationale Atherosclerotic lesions are known for their cellular heterogeneity, yet the molecular complexity within the cells of human plaques has not been fully assessed. Objective Using single-cell transcriptomics and chromatin accessibility, we gained a better understanding of the pathophysiology underlying human atherosclerosis. Methods and Results We performed single-cell RNA and single-cell ATAC sequencing on human carotid atherosclerotic plaques to define the cells at play and determine their transcriptomic and epigenomic characteristics. We identified 14 distinct cell populations including endothelial cells, smooth muscle cells, mast cells, B cells, myeloid cells, and T cells and identified multiple cellular activation states and suggested cellular interconversions. Within the endothelial cell population, we defined subsets with angiogenic capacity plus clear signs of endothelial to mesenchymal transition. CD4+ and CD8+ T cells showed activation-based subclasses, each with a gradual decline from a cytotoxic to a more quiescent phenotype. Myeloid cells included 2 populations of proinflammatory macrophages showing IL (interleukin) 1B or TNF (tumor necrosis factor) expression as well as a foam cell-like population expressing TREM2 (triggering receptor expressed on myeloid cells 2) and displaying a fibrosis-promoting phenotype. ATACseq data identified specific transcription factors associated with the myeloid subpopulation and T cell cytokine profiles underlying mutual activation between both cell types. Finally, cardiovascular disease susceptibility genes identified using public genome-wide association studies data were particularly enriched in lesional macrophages, endothelial, and smooth muscle cells. Conclusions This study provides a transcriptome-based cellular landscape of human atherosclerotic plaques and highlights cellular plasticity and intercellular communication at the site of disease. This detailed definition of cell communities at play in atherosclerosis will facilitate cell-based mapping of novel interventional targets with direct functional relevance for the treatment of human disease. GitHub A link to the public GitHub repository: https://github.com/CirculatoryHealth/MicroanatomyHumanPlaque_scRNAseq. This contains all scripts used for the data, which is pseudonymized and shared here. We also made a private GitHub repository (https://github.com/CirculatoryHealth/AE_TEMPLATE_SCRNASEQ_DATA_SHARE) to enable easy sharing with third parties, publicly or privately. Athero-Express Biobank Study The AE started in 2002 and now includes over 3,500 patients who underwent surgery to remove atherosclerotic plaques (endarterectomy) from one (or more) of their major arteries (majority carotids and femorals); this is further described here. The study design and staining protocols are described by Verhoeven et al.. Additional data Additional clinical data is available upon discussion and signing a Data Sharing Agreement (see Terms of Access). PlaqView In collaboration with the http://millerlab.org from the University of Virginia (USA) we created PlaqView.com. You can query any gene of interest in many carotid-plaque datasets, including ours. From our experience we know that usually this suffices most research questions and prevents the lengthy process of obtaining these data through a DSA

Perennial biomass cropping and use:Shaping the policy ecosystem in European countries

Demand for sustainably produced biomass is expected to increase with the need to provide renewable commodities, improve resource security, and reduce greenhouse gas emissions in line with COP26 commitments. Studies have demonstrated additional environmental benefits of using perennial biomass crops (PBCs), when produced appropriately, as a feedstock for the growing bioeconomy, including utilisation for bioenergy (with or without carbon capture and storage). PBCs can potentially contribute to Common Agricultural Policy (CAP) (2023-27) objectives provided they are carefully integrated into farming systems and landscapes. Despite significant research and development (R&D) investment over decades in herbaceous and coppiced woody PBCs, deployment has largely stagnated due to social, economic and policy uncertainties. This paper identifies the challenges in creating policies that are acceptable to all actors. Development will need to be informed by measurement, reporting and verification (MRV) of greenhouse gas emissions reductions and other environmental, economic and social metrics. It discusses interlinked issues that must be considered in the expansion of PBC production: i) available land; ii) yield potential; iii) integration into farming systems; iv) R&D requirements; v) utilisation options; and vi) market systems and the socio-economic environment. It makes policy recommendations that would enable greater PBC deployment: 1) incentivise farmers and land managers through specific policy measures, including carbon pricing, to allocate their less productive and less profitable land for uses which deliver demonstrable greenhouse gas reductions; 2) enable GHG mitigation markets to develop and offer secure contracts for commercial developers of verifiable low carbon bioenergy and bio-products; 3) support innovation in biomass utilisation value chains; and 4) continue long-term, strategic R&D and education for positive environmental, economic and social sustainability impacts

Perennial biomass cropping and use: Shaping the policy ecosystem in European countries

Abstract Demand for sustainably produced biomass is expected to increase with the need to provide renewable commodities, improve resource security and reduce greenhouse gas emissions in line with COP26 commitments. Studies have demonstrated additional environmental benefits of using perennial biomass crops (PBCs), when produced appropriately, as a feedstock for the growing bioeconomy, including utilisation for bioenergy (with or without carbon capture and storage). PBCs can potentially contribute to Common Agricultural Policy (CAP) (2023–27) objectives provided they are carefully integrated into farming systems and landscapes. Despite significant research and development (R&D) investment over decades in herbaceous and coppiced woody PBCs, deployment has largely stagnated due to social, economic and policy uncertainties. This paper identifies the challenges in creating policies that are acceptable to all actors. Development will need to be informed by measurement, reporting and verification (MRV) of greenhouse gas emissions reductions and other environmental, economic and social metrics. It discusses interlinked issues that must be considered in the expansion of PBC production: (i) available land; (ii) yield potential; (iii) integration into farming systems; (iv) R&D requirements; (v) utilisation options; and (vi) market systems and the socio‐economic environment. It makes policy recommendations that would enable greater PBC deployment: (1) incentivise farmers and land managers through specific policy measures, including carbon pricing, to allocate their less productive and less profitable land for uses which deliver demonstrable greenhouse gas reductions; (2) enable greenhouse gas mitigation markets to develop and offer secure contracts for commercial developers of verifiable low‐carbon bioenergy and bioproducts; (3) support innovation in biomass utilisation value chains; and (4) continue long‐term, strategic R&D and education for positive environmental, economic and social sustainability impacts

Building the Policy Ecosystem in Europe for Cultivation and use of Perennial Biomass Crops

Perennial biomass crops (PBCs) can potentially contribute to all ten Common Agricultural Policy (2023-27) objectives and up to eleven of the seventeen UN Sustainable Development Goals. This paper discusses interlinked issues that must be considered in the expansion of PBC production: i) available land; ii) yield potential; iii) integration into farming systems; iv) research and development requirements; v) utilisation options; and vi) market systems and the socio-economic environment. The challenge to create development pathways that are acceptable for all actors, relies on measurement, reporting and verification of greenhouse gas emissions reduction in combination with other environmental, economic and social aspects. This paper makes the following policy recommendations to enable greater PBC deployment: 1) incentivise farmers and land managers through specific policy measures, including carbon pricing, to allocate their less productive and less profitable land for uses which deliver demonstrable greenhouse gas reductions; 2) enable greenhouse gas mitigation markets to develop and offer secure contracts for commercial developers of verifiable low carbon bioenergy and bio-products; 3) support innovation in biomass utilisation value chains; and 4) continue long-term, strategic research and development and education for positive environmental, economic and social sustainability impacts.</p

Building the Policy Ecosystem in Europe for Cultivation and use of Perennial Biomass Crops

Perennial biomass crops (PBCs) can potentially contribute to all ten Common Agricultural Policy (2023-27) objectives and up to eleven of the seventeen UN Sustainable Development Goals. This paper discusses interlinked issues that must be considered in the expansion of PBC production: i) available land; ii) yield potential; iii) integration into farming systems; iv) research and development requirements; v) utilisation options; and vi) market systems and the socio-economic environment. The challenge to create development pathways that are acceptable for all actors, relies on measurement, reporting and verification of greenhouse gas emissions reduction in combination with other environmental, economic and social aspects. This paper makes the following policy recommendations to enable greater PBC deployment: 1) incentivise farmers and land managers through specific policy measures, including carbon pricing, to allocate their less productive and less profitable land for uses which deliver demonstrable greenhouse gas reductions; 2) enable greenhouse gas mitigation markets to develop and offer secure contracts for commercial developers of verifiable low carbon bioenergy and bio-products; 3) support innovation in biomass utilisation value chains; and 4) continue long-term, strategic research and development and education for positive environmental, economic and social sustainability impacts.</p