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

doi:10.1038/s41467-018-06684-2

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

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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.

Originele taal-2	Engels
Artikelnummer	4167
Tijdschrift	Nature Communications
Volume	9
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1038/s41467-018-06684-2
Status	Gepubliceerd - 2018

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Ormel, P. R., Vieira de Sá, R., van Bodegraven, E. J., Karst, H., Harschnitz, O., Sneeboer, M. A. M., Johansen, L. E., van Dijk, R. E., Scheefhals, N., Berdenis van Berlekom, A., Ribes Martínez, E., Kling, S., MacGillavry, H. D., van den Berg, L. H., Kahn, R. S., Hol, E. M., de Witte, L. D., & Pasterkamp, R. J. (2018). Microglia innately develop within cerebral organoids. Nature Communications, 9(1), Artikel 4167. https://doi.org/10.1038/s41467-018-06684-2

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title = "Microglia innately develop within cerebral organoids",

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.",

author = "Ormel, {Paul R} and {Vieira de S{\'a}}, Renata and {van Bodegraven}, {Emma J} and Henk Karst and Oliver Harschnitz and Sneeboer, {Marjolein A M} and Johansen, {Lill Eva} and {van Dijk}, {Roland E} and Nicky Scheefhals and {Berdenis van Berlekom}, Amber and {Ribes Mart{\'i}nez}, Eduardo and Sandra Kling and MacGillavry, {Harold D} and {van den Berg}, {Leonard H} and Kahn, {Ren{\'e} S} and Hol, {Elly M} and {de Witte}, {Lot D} and Pasterkamp, {R Jeroen}",

year = "2018",

doi = "10.1038/s41467-018-06684-2",

language = "English",

volume = "9",

journal = "Nature Communications",

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Ormel, PR, Vieira de Sá, R, van Bodegraven, EJ, Karst, H, Harschnitz, O, Sneeboer, MAM, Johansen, LE, van Dijk, RE, Scheefhals, N, Berdenis van Berlekom, A, Ribes Martínez, E, Kling, S, MacGillavry, HD, van den Berg, LH, Kahn, RS, Hol, EM, de Witte, LD & Pasterkamp, RJ 2018, 'Microglia innately develop within cerebral organoids', Nature Communications, vol. 9, nr. 1, 4167. https://doi.org/10.1038/s41467-018-06684-2

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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

PY - 2018

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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.

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SN - 2041-1723

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JO - Nature Communications

JF - Nature Communications

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Microglia innately develop within cerebral organoids

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