TY - JOUR
T1 - Microglia innately develop within cerebral organoids
AU - Ormel, Paul R.
AU - Vieira de Sá, Renata
AU - van Bodegraven, Emma J.
AU - Karst, Henk
AU - Harschnitz, Oliver
AU - Sneeboer, Marjolein A.M.
AU - Johansen, Lill Eva
AU - van Dijk, Roland E.
AU - Scheefhals, Nicky
AU - Berdenis van Berlekom, Amber
AU - Ribes Martínez, Eduardo
AU - Kling, Sandra
AU - MacGillavry, Harold D.
AU - van den Berg, Leonard H.
AU - Kahn, René S.
AU - Hol, Elly M.
AU - de Witte, Lot D.
AU - Pasterkamp, R. Jeroen
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85054592629&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-06684-2
DO - 10.1038/s41467-018-06684-2
M3 - Article
C2 - 30301888
SN - 2041-1723
VL - 9
JO - Nature Communications [E]
JF - Nature Communications [E]
IS - 1
M1 - 4167
ER -