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- Baeckdahl, Jesper, et al.
(författare)
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Spatial mapping reveals human adipocyte subpopulations with distinct sensitivities to insulin
- 2021
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 33:9, s. 1869-
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Tidskriftsartikel (refereegranskat)abstract
- The contribution of cellular heterogeneity and architecture to white adipose tissue (WAT) function is poorly understood. Herein, we combined spatially resolved transcriptional profiling with single-cell RNA sequencing and image analyses to map human WAT composition and structure. This identified 18 cell classes with unique propensities to form spatially organized homo-and heterotypic clusters. Of these, three constituted mature adipocytes that were similar in size, but distinct in their spatial arrangements and transcriptional profiles. Based on marker genes, we termed these Adipo(LEP), Adipo(PLIN), and Adipo(SAA). We confirmed, in independent datasets, that their respective gene profiles associated differently with both adipocyte and whole-body insulin sensitivity. Corroborating our observations, insulin stimulation in vivo by hyperinsulinemic-euglycemic clamp showed that only Adipo(PLIN) displayed a transcriptional response to insulin. Altogether, by mining this multimodal resource we identify that human WAT is composed of three classes of mature adipocytes, only one of which is insulin responsive.
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| 3. |
- Bergenstråhle, Joseph, et al.
(författare)
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Spatial transcriptomic profiling of RespiratorySyncytial Virus (RSV) infection
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Despite the fact that the human Respiratory Syncytial Virus (RSV) was first discoveredback in 1956, it remains one of the leading causes of morbidity and mortality inyoung children. Transcriptome-wide spatially resolved transcriptomics is a technologyunder rapid development that introduces a new modality for exploratory examinationof cellular behavior. With this modality, we examine how RSV infection changes thelocal cellular environment in the lung by infecting mice with RSV and comparing itto control samples four days after infection. We find viral presence in all compartmentsof the tissue, well-defined induced tertiary lymphoid tissue within some of thesamples, compartmentalized infiltration of innate immune cells, as well as functionalenrichment of airway epithelial repair pathways.
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| 4. |
- Bhalla, Nayanika, et al.
(författare)
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Spatial transcriptomics of human placentas reveal distinct RNA patterns associated with morphology and preeclampsia
- 2023
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Ingår i: Placenta. - : Elsevier BV. - 0143-4004 .- 1532-3102. ; 139, s. 213-216
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Tidskriftsartikel (refereegranskat)abstract
- Spatial transcriptomics (ST) maps RNA level patterns within a tissue. This technology has not been previously applied to human placental tissue. We demonstrate analysis of human placental samples with ST. Unsupervised clustering revealed that distinct RNA patterns were found corresponding to different morphological structures. Additionally, when focusing upon terminal villi and hemoglobin associated structures, RNA levels differed between placentas from full term healthy pregnancies and those complicated by preeclampsia. The results from this study can provide a benchmark for future ST studies in placenta.
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| 6. |
- Franzén, Gunilla, et al.
(författare)
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National implementation commission for Eurocode 7 for joint development of geotechnical engineering practice
- 2022
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Ingår i: Proceedings of 20th International Conference on Soil Mechanics and Geotechnical Engineering. - St Ives. ; , s. 4759-4764
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Konferensbidrag (refereegranskat)abstract
- The objective of this paper is to describe how upcoming design code revisions can be used to facilitate a national joint development of geotechnical engineering practice. The paper describes the Swedish experience with establishing a national implementation commission for the second generation of Eurocode 7. The purpose is to inspire others to take similar initiatives when new design codes and standards are introduced. The paper covers how stakeholders from all parts of the Swedish geotechnical construction industry established the implementation commission IEG 2.0 as a non-profit organization and how obstacles were solved. This includes financing and establishing an efficient work process to analyze the many upcoming changes to the Eurocode clauses. This in fact being the second Swedish implementation commission for Eurocode 7, the paper concludes that this procedure of working together in the industry is a great success, facilitating an increased competence among Swedish geotechnical engineers and therefore also increased competitiveness of the Swedish geotechnical construction industry.
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| 7. |
- Franzén, Lovisa, et al.
(författare)
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Spatially resolved transcriptomics of human and mouse fibrotic lung
- 2022
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 60
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by progressive and irreversible scarring of the lung tissue. Development of new efficacious and safe treatments is hampered by limited understanding of disease pathogenesis, lack of predictive preclinical models, and narrow therapeutic index of candidate drugs targeting complex biologies. Here, we tackle these aspects by generating spatially resolved transcriptomic maps of fibrotic lungs from clinical samples and a preclinical mouse model. We utilized the Visium platform to study parenchyma biopsies from four healthy lungs and regions of varying fibrotic severity from four IPF patient lungs. By mapping single cell RNA-seq data spatially, we were able to detect distinct fibroblast populations in different regions of the lesioned IPF lung, as well as the presence of various immune cell populations. To study lung fibrosis preclinically in vivo, the bleomycin mouse model is the most widely used alternative, although its translatability to human disease is disputed. Visium data from mouse lungs collected at two time points following bleomycin administration were generated, which allowed us to characterize the fibrotic lesions and inflammatory areas in their spatiotemporal context. In addition, mass spectrometry imaging was performed on adjacent tissue sections to provide paired spatial metabolomics. Herein, we have generated spatial maps of the lung fibrosis transcriptome from IPF lung biopsies and bleomycin-injured mouse lungs, providing an extensive resource to probe disease pathogenesis and animal model translatability.
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| 8. |
- Larsson, Ludvig, et al.
(författare)
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Semla : a versatile toolkit for spatially resolved transcriptomics analysis and visualization
- 2023
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 39:10
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Tidskriftsartikel (refereegranskat)abstract
- SUMMARY: Spatially resolved transcriptomics technologies generate gene expression data with retained positional information from a tissue section, often accompanied by a corresponding histological image. Computational tools should make it effortless to incorporate spatial information into data analyses and present analysis results in their histological context. Here, we present semla, an R package for processing, analysis, and visualization of spatially resolved transcriptomics data generated by the Visium platform, that includes interactive web applications for data exploration and tissue annotation. AVAILABILITY AND IMPLEMENTATION: The R package semla is available on GitHub (https://github.com/ludvigla/semla), under the MIT License, and deposited on Zenodo (https://doi.org/10.5281/zenodo.8321645). Documentation and tutorials with detailed descriptions of usage can be found at https://ludvigla.github.io/semla/.
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