SOX9-induced Generation of Functional Astrocytes Supporting Neuronal Maturation in an All-human System

• DOI: 10.1007/s12015-021-10179-x
• Publication Date: 2021-05-12T19:02:41Z
• Authors: Katrien Neyrinck; Johanna Van Den D...; Tim Vervliet; Jonathan De Smedt; Keimpe Wierda; Melissa Nijs; Tom Vanbokhoven; Astrid D’hondt; Mélanie Planque; Sarah-Maria Fendt; Pei-Yu Shih; Frederik Seibt; Juan Pita Almenar; Mohamed Kreir; Devesh Kumar; Vania Broccoli; Geert Bultynck; Andreas Ebneth; Alfredo Cabrera-S...; Catherine Verfaillie
• Keywords: Human brain

Abstract Astrocytes, the main supportive cell type of brain, show functional impairments upon ageing and in a broad spectrum neurological disorders. Limited access to human astroglia for pre-clinical studies has been major bottleneck delaying our understanding their role brain health disease. We demonstrate here that functionally mature astrocytes can be generated by SOX9 overexpression 6 days pluripotent stem (PSC)-derived neural progenitor cells. Inducible (i)SOX9-astrocytes display properties comparable primary comprising glutamate uptake, induced calcium responses cytokine/growth factor secretion. Importantly, electrophysiological iNGN2-neurons co-cultured with iSOX9-astrocytes are indistinguishable from gold-standard murine cultures. The high yield, fast timing possibility cryopreserve without losing makes them suitable scaled-up production high-throughput analyses. Our findings represent step forward an all-human iPSC-derived model drug development neuroscience towards reduction animal use biomedical research. Graphical