In vitro models of corticogenesis from pluripotent stem cells (PSCs) have greatly improved our understanding of human brain development and disease. Among these, 3D cortical organoid systems are able to recapitulate some aspects of in vivo cytoarchitecture of the developing cortex. Here, we tested three cortical organoid protocols for brain regional identity, cell type specificity and neuronal maturation. Overall, all protocols gave rise to organoids that displayed a time-dependent expression of neuronal maturation genes such as those involved in the establishment of synapses and neuronal function. Comparatively, guided differentiation methods without WNT activation generated the highest degree of cortical regional identity, whereas default conditions produced the broadest range of cell types such as neurons, astrocytes and hematopoietic-lineage-derived microglia cells. These results suggest that cortical organoid models produce diverse outcomes of brain regional identity and cell type specificity and emphasize the importance of selecting the correct model for the right application.

Brain Regional Identity and Cell Type Specificity Landscape of Human Cortical Organoid Models / M. Magni, B. Bossi, P. Conforti, M. Galimberti, F. Dezi, T. Lischetti, X. He, R.A. Barker, C. Zuccato, I. Espuny-Camacho, E. Cattaneo. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 23:21(2022 Oct 29), pp. 13159.1-13159.18. [10.3390/ijms232113159]

Brain Regional Identity and Cell Type Specificity Landscape of Human Cortical Organoid Models

P. Conforti;M. Galimberti;F. Dezi;T. Lischetti;C. Zuccato;E. Cattaneo
Ultimo
2022

Abstract

In vitro models of corticogenesis from pluripotent stem cells (PSCs) have greatly improved our understanding of human brain development and disease. Among these, 3D cortical organoid systems are able to recapitulate some aspects of in vivo cytoarchitecture of the developing cortex. Here, we tested three cortical organoid protocols for brain regional identity, cell type specificity and neuronal maturation. Overall, all protocols gave rise to organoids that displayed a time-dependent expression of neuronal maturation genes such as those involved in the establishment of synapses and neuronal function. Comparatively, guided differentiation methods without WNT activation generated the highest degree of cortical regional identity, whereas default conditions produced the broadest range of cell types such as neurons, astrocytes and hematopoietic-lineage-derived microglia cells. These results suggest that cortical organoid models produce diverse outcomes of brain regional identity and cell type specificity and emphasize the importance of selecting the correct model for the right application.
brain regional identity; cell type specificity; default and directed differentiation protocols; hPSC-derived 3D brain organoid models; neuronal maturation
Settore BIO/14 - Farmacologia
   Huntingtin hPSC: Unravelling huntingtin function in cortical and striatal human development (HUNTINGTIN hPSC)
   HUNTINGTIN hPSC
   EUROPEAN COMMISSION
   H2020
   799440

   European stem cell consortium for neural cell replacement, reprogramming and functional brain repair
   NEUROSTEMCELLREPAIR
   EUROPEAN COMMISSION
   FP7
   602278

   Integrated European omics research project for diagnosis and therapy in rare neuromuscular and neurodegenerative diseases
   NEUROMICS
   EUROPEAN COMMISSION
   FP7
   305121
29-ott-2022
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/949299
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