Microglia innately develop within cerebral organoids

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

doi:10.1038/s41467-018-06684-2

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.

Highlights

Cerebral organoids are 3D stem cell-derived models that can be utilized to study the human brain
Our results show that cells with a typical microglia molecular phenotype, morphology, and function are present in human cerebral organoids
Cerebral organoids were generated from human induced pluripotent stem cells (iPSCs) according to the protocol described by Lancaster et al.[17] with some minor modifications (Fig. 1a and Supplementary Table 1)

Summary

Introduction

Cerebral organoids are 3D stem cell-derived models that can be utilized to study the human brain. When comparing the data with the original iPSC lines and fibroblasts from the same donors, Fig. 1 Mesodermal progenitors develop into microglia-like cells within cerebral organoids. E IBA-1 immunostainings show distribution of microglia-like cells in cerebral organoids at day 31 and day 52 in culture.

Results

Conclusion