Untangling mechanisms for cerebellar neural specification using human pluripotent stem cell-derived organoids

2026 · doi:10.64898/2026.04.27.720597
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Keywords

human cerebellar organoids; pluripotent stem cells; Purkinje cells; deep cerebellar nuclei DCN; Granule cells GC

Abstract

[en] The cerebellum is one of the most complex structures of the brain composed of a high diversity of GABAergic and glutamatergic neurons. Whereas cerebellar biogenesis has been extensively studied in the mouse, an in-depth characterization of genes and pathways involved in cerebellar specification and maturation in the humans remains overlooked. Here, we used human pluripotent stem cells (hPSC)-derived cerebellar organoids (CRBOs) to study the temporal biogenesis of neuronal subtypes. Our results show that CRBOs acquire caudal neural tube identity at an early stage followed by a time-dependent expression of mature cerebellar neuronal markers in vitro, mimicking human neurodevelopment. CRBOs show the generation of both cerebellar excitatory and inhibitory neurons and the expression of glial cell markers, suggesting the generation of a high variety of cerebellar cell types in vitro. Further, in vitro CRBOs show expression of cerebellar disease associated genes, such as those related to ataxia. Our results establish CRBOs as a valuable platform to explore the mechanisms of human cerebellar development and related disorders. Disciplines : Biochemistry, biophysics & molecular biology Helgueta Romero, Sergio ; Université de Liège - ULiège > GIGA > GIGA Neurosciences - Molecular Regulation of Neurogenesis Bonafina, Antonela ; Université de Liège - ULiège > GIGA > GIGA Neurosciences - Molecular Regulation of Neurogenesis Olivié, Nicolas; Université de Liège > GIGA Neurosciences > Molecular Regulation of Neurogenesis Coumans, Bernard ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques Nguyen, Laurent ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques Espuny Camacho, Ira Mercedes ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques Language : English Title : Untangling mechanisms for cerebellar neural specification using human pluripotent stem cell-derived organoids Publication date : 30 April 2026 Publisher : BioRXiv Available on ORBi : since 04 June 2026 OpenCitations 0 OpenAlex citations 0

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