Journal
CELLS
Volume 11, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/cells11010124
Keywords
cerebral organoid; microglia; neurogenesis; neuronal function; development
Categories
Funding
- Academy of Finland [334801, 334800, 298071, 328287, 305516, 301234]
- University of Eastern Finland Doctoral programme in molecular medicine, the Finnish brain foundation, and the Finnish cultural foundation
- Academy of Finland (AKA) [328287, 334800, 334801, 298071, 301234, 305516, 334800, 334801, 298071, 301234, 305516, 328287] Funding Source: Academy of Finland (AKA)
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Human cerebral organoids derived from induced pluripotent stem cells can mimic the development of the cerebral cortex. By transplanting erythromyeloid progenitors differentiated from induced pluripotent stem cells, microglia-like cells can be formed in the organoids, promoting neuronal and network maturation through interaction with synaptic material.
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.
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