Microglia innately develop within cerebral organoids

被引:433
作者
Ormel, Paul R. [1 ,2 ]
de Sa, Renata Vieira [1 ]
van Bodegraven, Emma J. [1 ]
Karst, Henk [1 ]
Harschnitz, Oliver [1 ,3 ]
Sneeboer, Marjolein A. M. [1 ,2 ]
Johansen, Lill Eva [1 ,3 ]
van Dijk, Roland E. [1 ]
Scheefhals, Nicky [4 ]
van Berlekom, Amber Berdenis [1 ,2 ]
Martinez, Eduardo Ribes [1 ]
Kling, Sandra [1 ]
MacGillavry, Harold D. [4 ]
van den Berg, Leonard H. [3 ]
Kahn, Rene S. [2 ]
Hol, Elly M. [1 ,5 ]
de Witte, Lot D. [1 ,2 ]
Pasterkamp, R. Jeroen [1 ]
机构
[1] Univ Utrecht, UMCU, BCRM, Dept Translat Neurosci, POB 85500,Univ Weg 100, NL-3584 CG Utrecht, Netherlands
[2] Univ Utrecht, UMCU, BCRM, Dept Psychiat, POB 85500,Heidelberglaan 100, NL-3508 GA Utrecht, Netherlands
[3] Univ Utrecht, UMCU, BCRM, Dept Neurol, POB 85500,Heidelberglaan 100, NL-3508 GA Utrecht, Netherlands
[4] Univ Utrecht, Fac Sci, Dept Biol, Cell Biol, Padualaan 8, NL-3584 CH Utrecht, Netherlands
[5] Inst Royal Netherlands Acad Arts & Sci, Netherlands Inst Neurosci, Dept Neuroimmunol, Meibergdreef 47, NL-1105 BA Amsterdam, Netherlands
关键词
PLURIPOTENT STEM-CELLS; HUMAN BRAIN; REVEALS; DIFFERENTIATION; EXPRESSION; PROGENITOR; DISEASE; SYSTEMS; MOUSE; MODEL;
D O I
10.1038/s41467-018-06684-2
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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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页数:14
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