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.
Human cortical organoids expose a differential function of GSK3 on cortical neurogenesis / A. Lopez-Tobon, C.E. Villa, C. Cheroni, S. Trattaro, N. Caporale, P. Conforti, R. Iennaco, M. Lachgar, M.T. Rigoli, B. Marco De La Cruz, P. Lo Riso, E. Tenderini, F. Troglio, M. De Simone, I. Liste-Noya, G. Macino, M. Pagani, E. Cattaneo, G. Testa. - In: STEM CELL REPORTS. - ISSN 2213-6711. - 13:5(2019 Nov 12), pp. 847-861.
Titolo: | Human cortical organoids expose a differential function of GSK3 on cortical neurogenesis |
Autori: | TESTA, GIUSEPPE (Corresponding) |
Parole Chiave: | corticogenesis; GSK3; human brain organoids; outer radial glia; single cell transcriptomics |
Settore Scientifico Disciplinare: | Settore BIO/11 - Biologia Molecolare Settore BIO/10 - Biochimica Settore BIO/13 - Biologia Applicata Settore MED/04 - Patologia Generale Settore BIO/17 - Istologia |
Progetto: | Towards druggable targets in neurodevelopmental disorders: integrating single cell transcriptomics and reverse engineering in patient-derived cortical organoids Modeling Disease through Cell Reprogramming: a Translational Approach to the Pathogenesis of Syndromes Caused by Symmetrical Gene Dosage Imbalances Long non-coding RNAs of tumor infiltrating lymphocytes as novel anti-cancer therapeutic targets |
Data di pubblicazione: | 12-nov-2019 |
Rivista: | |
Tipologia: | Article (author) |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/j.stemcr.2019.09.005 |
Appare nelle tipologie: | 01 - Articolo su periodico |
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