Academic Bibliography
https://biblio.ugent.be/
Ghent University Academic Bibliography2000-01-01T00:00+00:001dailyDual targeting of MAPK and PI3K pathways unlocks redifferentiation of Braf-mutated thyroid cancer organoids
https://biblio.ugent.be/publication/01HRVW2DB5YSZ07TWCHFHEY21E
Lasolle, Helene Schiavo, Andrea Tourneur, Adrien Gillotay, Pierre de Faria da Fonseca, Barbara Ceolin, Lucieli Monestier, Olivier Aganahi, Benilda Chomette, Laura Kizys, Marina Malta LetroHaenebalcke, LievenPieters, TimGoossens, Steven Haigh, Jody Detours, Vincent Maia, Ana Luiza Silva Costagliola, Sabine Romitti, Mirian2024Thyroid cancer is the most common endocrine malignancy and several genetic events have been described to promote the development of thyroid carcinogenesis. Besides the effects of specific mutations on thyroid cancer development, the molecular mechanisms controlling tumorigenesis, tumor behavior, and drug resistance are still largely unknown. Cancer organoids have been proposed as a powerful tool to study aspects related to tumor development and progression and appear promising to test individual responses to therapies. Here, using mESC-derived thyroid organoids, we developed a Braf(V637E)-inducible model able to recapitulate the features of papillary thyroid cancer in vitro. Overexpression of the murine Braf(V637E) mutation, equivalent to Braf(V600E) in humans, rapidly triggers to MAPK activation, cell dedifferentiation, and disruption of follicular organization. Braf(V637E)-expressing organoids show a transcriptomic signature for p53, focal adhesion, ECM-receptor interactions, EMT, and inflammatory signaling pathways. Finally, PTC-like thyroid organoids were used for drug screening assays. The combination of MAPK and PI3K inhibitors reversed Braf(V637E) oncogene-promoted cell dedifferentiation while restoring thyroid follicle organization and function in vitro. Our results demonstrate that pluripotent stem cells-derived thyroid cancer organoids can mimic tumor development and features while providing an efficient tool for testing novel targeted therapies.application/pdfhttps://biblio.ugent.be/publication/01HRVW2DB5YSZ07TWCHFHEY21Ehttp://hdl.handle.net/1854/LU-01HRVW2DB5YSZ07TWCHFHEY21Ehttp://doi.org/10.1038/s41388-023-02889-yhttps://biblio.ugent.be/publication/01HRVW2DB5YSZ07TWCHFHEY21E/file/01HT2V44Q5GT3YYCVNH6ECA8AGengCreative Commons Attribution 4.0 International Public License (CC-BY 4.0)info:eu-repo/semantics/openAccessONCOGENEISSN: 0950-9232ISSN: 1476-5594Medicine and Health SciencesBiology and Life SciencesDual targeting of MAPK and PI3K pathways unlocks redifferentiation of Braf-mutated thyroid cancer organoidsjournalArticleinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionOTULIN maintains skin homeostasis by controlling keratinocyte death and stem cell identity
https://biblio.ugent.be/publication/8728696
Hoste, EstherLecomte, KimAnnusver, KarlVandamme, NielsRoels, JanaMaschalidi, SophiaVerboom, LienVikkula, Hanna-KaisaSze, MozesVan Hove, LisetteVerstaen, KevinMartens, ArneHochepied, TinoSaeys, YvanRavichandran, KodiKasper, Mariavan Loo, Geert2021OTULIN is a deubiquitinase for linear ubiquitin chains. Here the authors show, using genetic mouse models and single-cell RNA-sequencing, that deficiency of OTULIN in keratinocytes causes skin inflammation and verrucous carcinoma via the induction of keratinocyte death, thereby implicating a function of OTULIN in keratinocyte homeostasis. OTULIN is a deubiquitinase that specifically cleaves linear ubiquitin chains. Here we demonstrate that the ablation of Otulin selectively in keratinocytes causes inflammatory skin lesions that develop into verrucous carcinomas. Genetic deletion of Tnfr1, knockin expression of kinase-inactive Ripk1 or keratinocyte-specific deletion of Fadd and Mlkl completely rescues mice with OTULIN deficiency from dermatitis and tumorigenesis, thereby identifying keratinocyte cell death as the driving force for inflammation. Single-cell RNA-sequencing comparing non-lesional and lesional skin reveals changes in epidermal stem cell identity in OTULIN-deficient keratinocytes prior to substantial immune cell infiltration. Keratinocytes lacking OTULIN display a type-1 interferon and IL-1 beta response signature, and genetic or pharmacologic inhibition of these cytokines partially inhibits skin inflammation. Finally, expression of a hypomorphic mutant Otulin allele, previously shown to cause OTULIN-related autoinflammatory syndrome in humans, induces a similar inflammatory phenotype, thus supporting the importance of OTULIN for restraining skin inflammation and maintaining immune homeostasis.application/pdfhttps://biblio.ugent.be/publication/8728696http://hdl.handle.net/1854/LU-8728696http://doi.org/10.1038/s41467-021-25944-2https://biblio.ugent.be/publication/8728696/file/8728697engCreative Commons Attribution 4.0 International Public License (CC-BY 4.0)info:eu-repo/semantics/openAccessNATURE COMMUNICATIONSISSN: 2041-1723Biology and Life SciencesMedicine and Health SciencesNF-KAPPA-BLINEAR UBIQUITININFLAMMATIONRECEPTORSHARPINMICENECROPTOSISIL-1DEFICIENTMUTATIONSOTULIN maintains skin homeostasis by controlling keratinocyte death and stem cell identityjournalArticleinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionAutomated antibody dispensing to improve high-parameter flow cytometry throughput and analysis
https://biblio.ugent.be/publication/01HRY9VK5SHQV5ZFCGKKND5FDS
Bosteels, VictorVan Duyse, JulieRuyssinck, ElienVan Der Borght, KatrienNguyen, LongGavel, JannesJanssens, SophieVan Isterdael, Gert2024Over the past decade, the flow cytometry field has witnessed significant advancements in the number of fluorochromes that can be detected. This enables researchers to analyze more than 40 markers simultaneously on thousands of cells per second. However, with this increased complexity and multiplicity of markers, the manual dispensing of antibodies for flow cytometry experiments has become laborious, time-consuming, and prone to errors. An automated antibody dispensing system could provide a potential solution by enhancing the efficiency, and by improving data quality by faithfully dispensing the fluorochrome-conjugated antibodies and by enabling the easy addition of extra controls. In this study, a comprehensive comparison of different liquid handlers for dispensing fluorochrome-labeled antibodies was conducted for the preparation of flow cytometry stainings. The evaluation focused on key criteria including dispensing time, dead volume, and reliability of dispensing. After benchmarking, the I.DOT, a non-contact liquid handler, was selected and optimized in more detail. In the end, the I.DOT was able to prepare a 25-marker panel in 20 min, including the full stain, all FMOs and all single stain controls for cells and beads. Having all these controls improved the validation of the panel, visualization, and analysis of the data. Thus, automated antibody dispensing by dispensers such as the I.DOT reduces time and errors, enhances data quality, and can be easily integrated in an automated workflow to prepare samples for flow cytometry.application/pdfhttps://biblio.ugent.be/publication/01HRY9VK5SHQV5ZFCGKKND5FDShttp://hdl.handle.net/1854/LU-01HRY9VK5SHQV5ZFCGKKND5FDShttp://doi.org/10.1002/cyto.a.24835https://biblio.ugent.be/publication/01HRY9VK5SHQV5ZFCGKKND5FDS/file/01HRYR25FHQBAMBTJFH7J67ZW6engCreative Commons Attribution-NonCommercial 4.0 International Public License (CC BY-NC 4.0)info:eu-repo/semantics/openAccessCYTOMETRY PART AISSN: 1552-4922ISSN: 1552-4930Biology and Life SciencesMedicine and Health Sciencesimmune cell subsetsclinical trialsfixed whole bloodabsolute countshigh-dimensional flow cytometryimmunophenotypingAutomated antibody dispensing to improve high-parameter flow cytometry throughput and analysisjournalArticleinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion