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- Berglund, Emelie, et al.
(författare)
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Spatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Intra-tumor heterogeneity is one of the biggest challenges in cancer treatment today. Here we investigate tissue-wide gene expression heterogeneity throughout a multifocal prostate cancer using the spatial transcriptomics (ST) technology. Utilizing a novel approach for deconvolution, we analyze the transcriptomes of nearly 6750 tissue regions and extract distinct expression profiles for the different tissue components, such as stroma, normal and PIN glands, immune cells and cancer. We distinguish healthy and diseased areas and thereby provide insight into gene expression changes during the progression of prostate cancer. Compared to pathologist annotations, we delineate the extent of cancer foci more accurately, interestingly without link to histological changes. We identify gene expression gradients in stroma adjacent to tumor regions that allow for re-stratification of the tumor microenvironment. The establishment of these profiles is the first step towards an unbiased view of prostate cancer and can serve as a dictionary for future studies.
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- Chen, Xinsong, et al.
(författare)
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Breast cancer patient-derived whole-tumor cell culture model for efficient drug profiling and treatment response prediction
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 120:1
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer (BC) is a complex disease comprising multiple distinct subtypes with different genetic features and pathological characteristics. Although a large number of antineoplastic compounds have been approved for clinical use, patient-to-patient variability in drug response is frequently observed, highlighting the need for efficient treatment prediction for individualized therapy. Several patient-derived models have been established lately for the prediction of drug response. However, each of these models has its limitations that impede their clinical application. Here, we report that the whole-tumor cell culture (WTC) ex vivo model could be stably established from all breast tumors with a high success rate (98 out of 116), and it could reassemble the parental tumors with the endogenous microenvironment. We observed strong clinical associations and predictive values from the investigation of a broad range of BC therapies with WTCs derived from a patient cohort. The accuracy was further supported by the correlation between WTC-based test results and patients' clinical responses in a separate validation study, where the neoadjuvant treatment regimens of 15 BC patients were mimicked. Collectively, the WTC model allows us to accomplish personalized drug testing within 10 d, even for small-sized tumors, highlighting its potential for individualized BC therapy. Furthermore, coupled with genomic and transcriptomic analyses, WTC-based testing can also help to stratify specific patient groups for assignment into appropriate clinical trials, as well as validate potential biomarkers during drug development.
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| 4. |
- Engblom, Camilla, et al.
(författare)
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Spatial transcriptomics of B cell and T cell receptors reveals lymphocyte clonal dynamics
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 382:6675, s. 8486-
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Tidskriftsartikel (refereegranskat)abstract
- The spatial distribution of lymphocyte clones within tissues is critical to their development, selection, and expansion. We have developed spatial transcriptomics of variable, diversity, and joining (VDJ) sequences (Spatial VDJ), a method that maps B cell and T cell receptor sequences in human tissue sections. Spatial VDJ captures lymphocyte clones that match canonical B and T cell distributions and amplifies clonal sequences confirmed by orthogonal methods. We found spatial congruency between paired receptor chains, developed a computational framework to predict receptor pairs, and linked the expansion of distinct B cell clones to different tumor-associated gene expression programs. Spatial VDJ delineates B cell clonal diversity and lineage trajectories within their anatomical niche. Thus, Spatial VDJ captures lymphocyte spatial clonal architecture across tissues, providing a platform to harness clonal sequences for therapy.
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| 7. |
- Malmström, Mikael, PhD, 1982-, et al.
(författare)
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Non-destructive ultrasonic measurement of residual stress in metallic materials
- 2024
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Ingår i: Proceedings of 20th WCNDT. - Incheon, South Korea : KSNT.
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Konferensbidrag (refereegranskat)abstract
- Residual stresses in metallic materials occur to a varying degree depending on the process stages and different process parameters. The residual stresses may become problematic not only when the material is further processed down-stream in the value chain, but also affects the performance of the final product negatively due to impaired fatigue properties. Today there is no measuring technique that is fast, reliable, and robust enough to measure the residual stresses, which impede process developments due to that no feedback to the operators is available. The overall purpose of the project is to develop a new measuring technique for detection of varying levels of residual stress in the material, which would lead to a drastically increased knowledge on how different processes and parameters affects the final stress state. By using a non-destructive method suited for on-line monitoring, the dynamic changes can be evaluated and enable real-time feedback to the operators. This will be achieved by developing a model that correlates the birefringence in ultrasonic data to the stress level and applied as an electro-magnetic acoustic transducer (EMAT) based on-line measurements demonstrator, in the steel works environment. The non-contact EMAT probe will be installed close to the plate leveling to measure the ultrasonics response before and after leveling. The results from this on-line measurement campaign will be presented.
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| 8. |
- Mold, Jeff E., et al.
(författare)
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Clonally heritable gene expression imparts a layer of diversity within cell types
- 2024
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Ingår i: Cell systems. - : Elsevier BV. - 2405-4720. ; 15:2, s. 149-
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Tidskriftsartikel (refereegranskat)abstract
- Cell types can be classified according to shared patterns of transcription. Non-genetic variability among individual cells of the same type has been ascribed to stochastic transcriptional bursting and transient cell states. Using high-coverage single-cell RNA profiling, we asked whether long-term, heritable differences in gene expression can impart diversity within cells of the same type. Studying clonal human lymphocytes and mouse brain cells, we uncovered a vast diversity of heritable gene expression patterns among different clones of cells of the same type in vivo. We combined chromatin accessibility and RNA profiling on different lymphocyte clones to reveal thousands of regulatory regions exhibiting interclonal variation, which could be directly linked to interclonal variation in gene expression. Our findings identify a source of cellular diversity, which may have important implications for how cellular populations are shaped by selective processes in development, aging, and disease. A record of this paper's transparent peer review process is included in the supplemental information.
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| 10. |
- Rosengren, Annika, 1951, et al.
(författare)
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COVID-19 in people aged 18–64 in Sweden in the first year of the pandemic: Key factors for severe disease and death
- 2022
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Ingår i: Global Epidemiology. - : Elsevier BV. - 2590-1133. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies on risk factors for severe COVID-19 in people of working age have generally not included non-working persons or established population attributable fractions (PAFs) for occupational and other factors. Objectives: We describe the effect of job-related, sociodemographic, and other exposures on the incidence, relative risks and PAFs of severe COVID-19 in individuals aged 18–64. Methods: We conducted a registry-based study in Swedish citizens aged 18–64 from 1 January 2020 to 1 February 2021 with respect to COVID-19-related hospitalizations and death. Results: Of 6,205,459 persons, 272,043 (7.5%) were registered as infected, 3399 (0.05%) needed intensive care, and 620 (0.01%) died, with an estimated case fatality rate of 0.06% over the last 4-month period when testing was adequate. Non-Nordic origin was associated with a RR for need of intensive care of 3·13, 95%CI 2·91–3·36, and a PAF of 32·2% after adjustment for age, sex, work, region and comorbidities. In a second model with occupation as main exposure, and adjusted for age, sex, region, comorbidities and origin, essential workers had an RR of 1·51, 95%CI, 1·35–1·6, blue-collar workers 1·18, 95%CI 1·06–1·31, school staff 1·21, 95%CI 1·01–1·46, and health and social care workers 1·89, 95%CI 1·67–2·135) compared with people able to work from home, with altogether about 13% of the PAF associated with these occupations. Essential workers and blue-collar workers, but no other job categories had higher risk of death, adjusted RRs of 1·79, 95%CI 1·34–2·38 and 1·37, 95%CI 1·04–1·81, with adjusted PAFs of altogether 9%. Conclusion: Among people of working age in Sweden, overall mortality and case fatality were low. Occupations that require physical presence at work were associated with elevated risk of needing intensive care for COVID-19, with 14% cases attributable to this factor, and 9% of deaths.
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