ORCID Profile
0000-0001-5759-7336
Current Organisations
University of Eastern Finland
,
School of Health Technologies of Lisbon
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Publisher: MDPI AG
Date: 30-12-2021
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-cl electrophysiological recordings show that the microglia-like population supported the emergence of more mature and ersified 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.
Publisher: Cold Spring Harbor Laboratory
Date: 09-12-2020
DOI: 10.1101/2020.12.08.416388
Abstract: Human stem cell-derived brain organoids provide a physiologically relevant in vitro 3D brain model for studies of neurological development that are unique to the human nervous system. Prior studies have reported protocols that support the maturation of microglia from mesodermal progenitors leading to innately developing microglia within the organoids. However, although microglia are known to support neuronal development in rodents, none of the previous studies have reported what is the impact of microglia on neuronal growth and maturation in human brain organoids. Here we show that incorporating microglial progenitors into the developing organoid supports neuronal maturation, the emergence of neurons capable of firing repetitive action potentials and the appearance of synaptic and neuronal bursting activity. Immunocompetent organoids enable experimental strategies for interrogating fundamental questions on microglial and neuronal ersity and function during human brain development.
Publisher: Public Library of Science (PLoS)
Date: 31-12-2013
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Margarida Eiras.