Details

Autor(en) / Beteiligte

• Neyrinck, Katrien
• Van Den Daele, Johanna
• Vervliet, Tim
• De Smedt, Jonathan
• Wierda, Keimpe
• Nijs, Melissa
• Vanbokhoven, Tom
• D’hondt, Astrid
• Planque, Mélanie
• Fendt, Sarah-Maria
• Shih, Pei-Yu
• Seibt, Frederik
• Almenar, Juan Pita
• Kreir, Mohamed
• Kumar, Devesh
• Broccoli, Vania
• Bultynck, Geert
• Ebneth, Andreas
• Cabrera-Socorro, Alfredo
• Verfaillie, Catherine

Titel

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

Ist Teil von

• Stem cell reviews and reports, 2021-10, Vol.17 (5), p.1855-1873

Ort / Verlag

New York: Springer US

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

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