Fagerlund, Ilkka and Dougalis, Antonios and Shakirzyanova, Anastasia and Gómez-Budia, Mireia and Pelkonen, Anssi and Konttinen, Henna and Ohtonen, Sohvi and Fazaludeen, Mohammad Feroze and Koskuvi, Marja and Kuusisto, Johanna and Hernández, Damián and Pebay, Alice and Koistinaho, Jari and Rauramaa, Tuomas and Lehtonen, Šárka and Korhonen, Paula and Malm, Tarja (2021) Microglia-like Cells Promote Neuronal Functions in Cerebral Organoids. Cells, 11 (1). p. 124. ISSN 2073-4409
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Abstract
Human cerebral organoids, derived from induced pluripotent stem cells, offer a unique in vitro research window to the development of the cerebral cortex. However, a key player in the developing brain, the microglia, do not natively emerge in cerebral organoids. Here we show that erythromyeloid progenitors (EMPs), differentiated from induced pluripotent stem cells, migrate to cerebral organoids, and mature into microglia-like cells and interact with synaptic material. Patch-clamp electrophysiological recordings show that the microglia-like population supported the emergence of more mature and diversified neuronal phenotypes displaying repetitive firing of action potentials, low-threshold spikes and synaptic activity, while multielectrode array recordings revealed spontaneous bursting activity and increased power of gamma-band oscillations upon pharmacological challenge with NMDA. To conclude, microglia-like cells within the organoids promote neuronal and network maturation and recapitulate some aspects of microglia-neuron co-development in vivo, indicating that cerebral organoids could be a useful biorealistic human in vitro platform for studying microglia-neuron interactions.
Item Type: | Article |
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Subjects: | GO STM Archive > Biological Science |
Depositing User: | Unnamed user with email support@gostmarchive.com |
Date Deposited: | 05 Jan 2023 10:23 |
Last Modified: | 02 May 2024 05:57 |
URI: | http://journal.openarchivescholar.com/id/eprint/2 |