Microglia innately develop within cerebral organoids

Paul R. Ormel, Renata Vieira de Sá, Emma J. Bodegraven, Henk Karst, Oliver Harschnitz, Marjolein A. M. Sneeboer, Lill Eva Johansen, Roland E. Dijk, Nicky Scheefhals, Amber Berdenis van Berlekom, Eduardo Ribes Martínez, Sandra Kling, Harold D. MacGillavry, Leonard H. Berg, René S. Kahn, Elly M. Hol, Lot D. Witte () and R. Jeroen Pasterkamp
Additional contact information
Paul R. Ormel: University Medical Center Utrecht (BCRM-UMCU), Utrecht University
Renata Vieira de Sá: University Medical Center Utrecht (BCRM-UMCU), Utrecht University
Emma J. Bodegraven: University Medical Center Utrecht (BCRM-UMCU), Utrecht University
Henk Karst: University Medical Center Utrecht (BCRM-UMCU), Utrecht University
Oliver Harschnitz: University Medical Center Utrecht (BCRM-UMCU), Utrecht University
Marjolein A. M. Sneeboer: University Medical Center Utrecht (BCRM-UMCU), Utrecht University
Lill Eva Johansen: University Medical Center Utrecht (BCRM-UMCU), Utrecht University
Roland E. Dijk: University Medical Center Utrecht (BCRM-UMCU), Utrecht University
Nicky Scheefhals: Utrecht University, Padualaan 8
Amber Berdenis van Berlekom: University Medical Center Utrecht (BCRM-UMCU), Utrecht University
Eduardo Ribes Martínez: University Medical Center Utrecht (BCRM-UMCU), Utrecht University
Sandra Kling: University Medical Center Utrecht (BCRM-UMCU), Utrecht University
Harold D. MacGillavry: Utrecht University, Padualaan 8
Leonard H. Berg: Utrecht University
René S. Kahn: Utrecht University
Elly M. Hol: University Medical Center Utrecht (BCRM-UMCU), Utrecht University
Lot D. Witte: University Medical Center Utrecht (BCRM-UMCU), Utrecht University
R. Jeroen Pasterkamp: University Medical Center Utrecht (BCRM-UMCU), Utrecht University

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06684-2

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