Deakin University
Browse
hernandez-microglia-likecells-2022.pdf (3.59 MB)

Microglia-like cells promote neuronal functions in cerebral organoids

Download (3.59 MB)
Version 3 2024-06-19, 09:30
Version 2 2024-05-30, 14:22
Version 1 2022-03-10, 08:11
journal contribution
posted on 2024-06-19, 09:30 authored by I Fagerlund, A Dougalis, A Shakirzyanova, M Gómez-Budia, A Pelkonen, H Konttinen, S Ohtonen, MF Fazaludeen, M Koskuvi, J Kuusisto, Damian HernandezDamian Hernandez, A Pebay, J Koistinaho, T Rauramaa, Š Lehtonen, P Korhonen, T Malm
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.

History

Journal

Cells

Volume

11

Article number

124

Pagination

1-23

Location

Basel, Switzerland

Open access

  • Yes

ISSN

2073-4409

eISSN

2073-4409

Language

English

Publication classification

C1 Refereed article in a scholarly journal

Issue

1

Publisher

MDPI