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dc.contributor.authorLópez-Tobón, Alejandro
dc.contributor.authorVilla, Carlo Emanuele
dc.contributor.authorCheroni, Cristina
dc.contributor.authorTrattaro, Sebastiano
dc.contributor.authorCaporale, Nicolò
dc.contributor.authorConforti, Paola
dc.contributor.authorIennaco, Raffaele
dc.contributor.authorLachgar-Ruiz, Maria 
dc.contributor.authorRigoli, Marco Tullio
dc.contributor.authorMarcó de la Cruz, Berta
dc.contributor.authorLo Riso, Pietro
dc.contributor.authorTenderini, Erika
dc.contributor.authorTroglio, Flavia
dc.contributor.authorDe Simone, Marco
dc.contributor.authorListe-Noya, Isabel 
dc.contributor.authorMacino, Giuseppe
dc.contributor.authorPagani, Massimiliano
dc.contributor.authorCattaneo, Elena
dc.contributor.authorTesta, Giuseppe
dc.identifier.citationStem Cell Reports. 2019 Nov 12;13(5):847-861.es_ES
dc.description.abstractThe 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.es_ES
dc.description.sponsorshipThis 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 within the European School of Molecular Medicine (SEMM). M.P. is a founder, shareholder and a member of the scientific advisory board of CheckmAb s.r.l. We are grateful to Pierre-Luc Germain for providing scripts that facilitated the analysis, to Andreas Püschel (University of Münster, Germany) for critical comments on the introduction, to Stefano Piccolo (University of Padua, Italy) for sharing of expertise, and to Federica Pisati from the tissue processing facility and the IEO genomic unit team.es_ES
dc.publisherElsevier es_ES
dc.subjectHuman brain organoidses_ES
dc.subjectOuter radial gliaes_ES
dc.subjectSingle cell transcriptomicses_ES
dc.titleHuman Cortical Organoids Expose a Differential Function of GSK3 on Cortical Neurogenesises_ES
dc.typejournal articlees_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.contributor.funderItalian Association for Cancer Research 
dc.contributor.funderConsiglio Nazionale delle Ricerche (Italia) 
dc.contributor.funderFondazione Cariplo 
dc.contributor.funderEuropean Research Council 
dc.contributor.funderUnión Europea 
dc.identifier.journalStem cell reportses_ES
dc.repisalud.centroISCIII::Unidad Funcional de Investigación de Enfermedades Crónicas (UFIEC)es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/IG 2014-2018es_ES
dc.rights.accessRightsopen accesses_ES

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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
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