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Human Cortical Organoids Expose a Differential Function of GSK3 on Cortical Neurogenesis

التفاصيل البيبلوغرافية
العنوان: Human Cortical Organoids Expose a Differential Function of GSK3 on Cortical Neurogenesis
المؤلفون: López-Tobón, Alejandro, Villa, Carlo Emanuele, Cheroni, Cristina, Trattaro, Sebastiano, Caporale, Nicolò, Conforti, Paola, Iennaco, Raffaele, Lachgar-Ruiz, Maria, Rigoli, Marco Tullio, Marcó de la Cruz, Berta, Lo Riso, Pietro, Tenderini, Erika, Troglio, Flavia, De Simone, Marco, Liste-Noya, Isabel, Macino, Giuseppe, Pagani, Massimiliano, Cattaneo, Elena, Testa, Giuseppe
المساهمون: Italian Association for Cancer Research, Consiglio Nazionale delle Ricerche (Italia), Fondazione Cariplo, Unión Europea. Comisión Europea. European Research Council (ERC), Unión Europea
بيانات النشر: Elsevier
سنة النشر: 2019
المجموعة: REPISALUD (REPositorio Institucional en SALUD del Instituto de Salud Carlos III - ISCIII)
مصطلحات موضوعية: GSK3, Corticogenesis, Human brain organoids, Outer radial glia, Single cell transcriptomics
الوصف: The regulation of the proliferation and polarity of neural progenitors is crucial for the development of the brain cortex. Animal studies have implicated glycogen synthase kinase 3 (GSK3) as a pivotal regulator of both proliferation and polarity, yet the functional relevance of its signaling for the unique features of human corticogenesis remains to be elucidated. We harnessed human cortical brain organoids to probe the longitudinal impact of GSK3 inhibition through multiple developmental stages. Chronic GSK3 inhibition increased the proliferation of neural progenitors and caused massive derangement of cortical tissue architecture. Single-cell transcriptome profiling revealed a direct impact on early neurogenesis and uncovered a selective role of GSK3 in the regulation of glutamatergic lineages and outer radial glia output. Our dissection of the GSK3-dependent transcriptional network in human corticogenesis underscores the robustness of the programs determining neuronal identity independent of tissue architecture. ; This work was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) (IG 2014-2018 to G.T.); EPIGEN Flagship Project of the Italian National Research Council (CNR) (to G.T., G.M., and M.P.); the European Research Council (ERC DISEASEAVATARS no. 616441 to G.T.); Fondazione Cariplo (2017-0886 to A.L.-T.); EDC-MixRisk, European Union's Horizon 2020 research and innovation programme (Grant No 634880. to G.T., C.C., and N.C.); ENDpoiNTs, European Union's Horizon 2020 research and innovation programme (Grant No 825759. to G.T. and C.C.); European Commission H2020 Project Joint Programme – Neurodegenerative Disease Research (JPND) ModelPolyQ (Grant No 643417” to R.I., P.C., and E.C.); Fondazione Italiana per la Ricerca sul Cancro (FIRC) and Fondazione Istituto Europeo di Oncologia - Centro Cardiologico Monzino (IEO-CCM) (to P.L.R.); the AIRC grant no. IG2016-ID18575 (to M.P.) and the ERC Consolidator grant no. 617978 (to M.P.) and the IEO Single Cell Program. S.T. and N.C. are PhD students ...
نوع الوثيقة: article in journal/newspaper
اللغة: English
تدمد: 2213-6711
Relation: https://doi.org/10.1016/j.stemcr.2019.09.005; info:eu-repo/grantAgreement/ES/IG 2014-2018; info:eu-repo/grantAgreement/ES/616441; info:eu-repo/grantAgreement/ES/2017-0886; info:eu-repo/grantAgreement/ES/634880; info:eu-repo/grantAgreement/ES/825759; info:eu-repo/grantAgreement/ES/643417; info:eu-repo/grantAgreement/ES/IG2016-ID18575; info:eu-repo/grantAgreement/ES/617978; Stem Cell Reports. 2019 Nov 12;13(5):847-861.; http://hdl.handle.net/20.500.12105/9091; Stem cell reports
DOI: 10.1016/j.stemcr.2019.09.005
الاتاحة: https://hdl.handle.net/20.500.12105/9091
https://doi.org/10.1016/j.stemcr.2019.09.005
Rights: http://creativecommons.org/licenses/by-nc-nd/4.0/ ; Attribution-NonCommercial-NoDerivatives 4.0 Internacional ; open access
رقم الانضمام: edsbas.4B8329E1
قاعدة البيانات: BASE
الوصف
تدمد:22136711
DOI:10.1016/j.stemcr.2019.09.005