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Nat Commun. 2018 Oct 9;9(1):4167. doi: 10.1038/s41467-018-06684-2.

Microglia innately develop within cerebral organoids.

Author information

1
Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht (BCRM-UMCU), Utrecht University, P.O. Box 85500, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.
2
Department of Psychiatry, BCRM-UMCU, Utrecht University, P.O. Box 85500, Heidelberglaan 100, 3508 GA, Utrecht, The Netherlands.
3
Department of Neurology, BCRM-UMCU, Utrecht University, P.O. Box 85500, Heidelberglaan 100, 3508 GA, Utrecht, The Netherlands.
4
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands.
5
Department of Neuroimmunology, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands.
6
Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht (BCRM-UMCU), Utrecht University, P.O. Box 85500, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands. L.D.deWitte@umcutrecht.nl.
7
Department of Psychiatry, BCRM-UMCU, Utrecht University, P.O. Box 85500, Heidelberglaan 100, 3508 GA, Utrecht, The Netherlands. L.D.deWitte@umcutrecht.nl.

Abstract

Cerebral organoids are 3D stem cell-derived models that can be utilized to study the human brain. The current consensus is that cerebral organoids consist of cells derived from the neuroectodermal lineage. This limits their value and applicability, as mesodermal-derived microglia are important players in neural development and disease. Remarkably, here we show that microglia can innately develop within a cerebral organoid model and display their characteristic ramified morphology. The transcriptome and response to inflammatory stimulation of these organoid-grown microglia closely mimic the transcriptome and response of adult microglia acutely isolated from post mortem human brain tissue. In addition, organoid-grown microglia mediate phagocytosis and synaptic material is detected inside them. In all, our study characterizes a microglia-containing organoid model that represents a valuable tool for studying the interplay between microglia, macroglia, and neurons in human brain development and disease.

PMID:
30301888
PMCID:
PMC6177485
DOI:
10.1038/s41467-018-06684-2
[Indexed for MEDLINE]
Free PMC Article

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