Generation of Urine-Derived Induced Pluripotent Stem Cells and Cerebral Organoids for Modeling Down Syndrome

Autor(es)

Teles e Silva, Andre Luiz ; Yokota, Bruno Yukio ; Sertie, Andrea Laurato ; Zampieri, Bruna Lancia

• Tipo de documento: Artigo Científico
• Fonte: STEM CELL REVIEWS AND REPORTS; v. N/A, p. 8-pg., 2023-01-18.

Resumo

Down syndrome (DS, or trisomy 21, T21), is the most common genetic cause of intellectual disability. Alterations in the complex process of cerebral cortex development contribute to the neurological deficits in DS, although the underlying molecular and cellular mechanisms are not completely understood. Human cerebral organoids (COs) derived from three-dimensional (3D) cultures of induced pluripotent stem cells (iPSCs) provide a new avenue for gaining a better understanding of DS neuropathology. In this study, we aimed to generate iPSCs from individuals with DS (T21-iPSCs) and euploid controls using urine-derived cells, which can be easily and noninvasively obtained from most individuals, and examine their ability to differentiate into neurons and astrocytes grown in monolayer cultures, as well as into 3D COs. We employed nonintegrating episomal vectors to generate urine-derived iPSC lines, and a simple-to-use system to produce COs with forebrain identity. We observed that both T21 and control urine-derived iPSC lines successfully differentiate into neurons and astrocytes in monolayer, as well as into COs that recapitulate early features of human cortical development, including organization of neural progenitor zones, programmed differentiation of excitatory and inhibitory neurons, and upper-and deep-layer cortical neurons as well as astrocytes. Our findings demonstrate for the first time the suitability of using urine-derived iPSC lines to produce COs for modeling DS. (AU)

• Processo FAPESP: 19/08655-2 - Estudo funcional de variantes genéticas raras no Transtorno do Espectro Autista: um modelo oligogênico de herança?
• Beneficiário: Andréa Laurato Sertié
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 21/14491-2 - Investigação dos mecanismos moleculares e celulares da herança oligogênica no Transtorno do espectro autista
• Beneficiário: Andréa Laurato Sertié
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/04859-2 - Produção de células-tronco pluripotentes induzidas a partir de células epiteliais descamadas na urina de indivíduos com Síndrome de Down
• Beneficiário: Bruna Lancia Zampieri
• Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores
• Processo FAPESP: 18/15371-8 - Produção de células-tronco pluripotentes induzidas a partir de células epiteliais descamadas na urina de indivíduos com Síndrome de Down
• Beneficiário: Bruna Lancia Zampieri
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores