Microglia innately develop within cerebral organoids

Paul R. Ormel, Renata Vieira de Sá, Emma J. van Bodegraven, Henk Karst, Oliver Harschnitz, Marjolein A.M. Sneeboer, Lill Eva Johansen, Roland E. van Dijk, Nicky Scheefhals, Amber Berdenis van Berlekom, Eduardo Ribes Martínez, Sandra Kling, Harold D. MacGillavry, Leonard H. van den Berg, René S. Kahn, Elly M. Hol, Lot D. de Witte*, R. Jeroen Pasterkamp

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article number4167
JournalNature Communications [E]
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

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