Stem-cell-derived human microglia transplanted in mouse brain to study human disease
Stem-cell-derived human microglia transplanted in mouse brain to study human disease
Although genetics highlights the role of microglia in Alzheimer's disease, one-third of putative Alzheimer's disease risk genes lack adequate mouse orthologs. Here we successfully engraft human microglia derived from embryonic stem cells in the mouse brain. The cells recapitulate transcriptionally human primary microglia ex vivo and show expression of human-specific Alzheimer's disease risk genes. Oligomeric amyloid-β induces a divergent response in human versus mouse microglia. This model can be used to study the role of microglia in neurological diseases.
Alzheimer Disease/genetics, Amyloid beta-Peptides/pharmacology, Animals, Cell Differentiation, Embryonic Stem Cells/cytology, Female, Humans, Male, Mice, Mice, Transgenic, Microglia/drug effects, Transcriptome
2111-2116
Mancuso, Renzo
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Van Den Daele, Johanna
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Fattorelli, Nicola
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Wolfs, Leen
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Balusu, Sriram
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Burton, Oliver
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Liston, Adrian
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Sierksma, Annerieke
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Fourne, Yannick
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Poovathingal, Suresh
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Arranz-Mendiguren, Amaia
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Sala Frigerio, Carlo
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Claes, Christel
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Serneels, Lutgarde
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Theys, Tom
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Perry, V Hugh
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Verfaillie, Catherine
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Fiers, Mark
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De Strooper, Bart
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December 2019
Mancuso, Renzo
05786562-a993-4e37-926e-3c1fcf50b36d
Van Den Daele, Johanna
bd3e0de9-750b-407c-9c98-bfa29b50201e
Fattorelli, Nicola
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Wolfs, Leen
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Balusu, Sriram
0af8bdbf-6fd0-4c46-966c-b89235466d87
Burton, Oliver
71c0d7be-580f-4a6f-a8a2-47a4596e02f3
Liston, Adrian
6b943804-e074-43e1-9941-768004e95042
Sierksma, Annerieke
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Fourne, Yannick
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Poovathingal, Suresh
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Arranz-Mendiguren, Amaia
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Sala Frigerio, Carlo
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Claes, Christel
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Serneels, Lutgarde
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Theys, Tom
d442e1fc-5ec7-4aaa-8b01-951fd579793d
Perry, V Hugh
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Verfaillie, Catherine
fe5eae96-27e6-4024-a6f5-9ad0cd56b41b
Fiers, Mark
36374677-3e36-4eb6-91da-6c4a3b2ad3ad
De Strooper, Bart
1df9ea7c-2c32-4598-912d-39feeb77368f
Mancuso, Renzo, Van Den Daele, Johanna, Fattorelli, Nicola, Wolfs, Leen, Balusu, Sriram, Burton, Oliver, Liston, Adrian, Sierksma, Annerieke, Fourne, Yannick, Poovathingal, Suresh, Arranz-Mendiguren, Amaia, Sala Frigerio, Carlo, Claes, Christel, Serneels, Lutgarde, Theys, Tom, Perry, V Hugh, Verfaillie, Catherine, Fiers, Mark and De Strooper, Bart
(2019)
Stem-cell-derived human microglia transplanted in mouse brain to study human disease.
Nature Neuroscience, 22 (12), .
(doi:10.1101/562561).
Abstract
Although genetics highlights the role of microglia in Alzheimer's disease, one-third of putative Alzheimer's disease risk genes lack adequate mouse orthologs. Here we successfully engraft human microglia derived from embryonic stem cells in the mouse brain. The cells recapitulate transcriptionally human primary microglia ex vivo and show expression of human-specific Alzheimer's disease risk genes. Oligomeric amyloid-β induces a divergent response in human versus mouse microglia. This model can be used to study the role of microglia in neurological diseases.
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More information
Accepted/In Press date: 26 September 2019
e-pub ahead of print date: 28 October 2019
Published date: December 2019
Keywords:
Alzheimer Disease/genetics, Amyloid beta-Peptides/pharmacology, Animals, Cell Differentiation, Embryonic Stem Cells/cytology, Female, Humans, Male, Mice, Mice, Transgenic, Microglia/drug effects, Transcriptome
Identifiers
Local EPrints ID: 438668
URI: http://eprints.soton.ac.uk/id/eprint/438668
ISSN: 1097-6256
PURE UUID: 0fc7816e-b52b-4e54-9e44-c5bea90441bc
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Date deposited: 20 Mar 2020 17:30
Last modified: 16 Mar 2024 06:23
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Contributors
Author:
Renzo Mancuso
Author:
Johanna Van Den Daele
Author:
Nicola Fattorelli
Author:
Leen Wolfs
Author:
Sriram Balusu
Author:
Oliver Burton
Author:
Adrian Liston
Author:
Annerieke Sierksma
Author:
Yannick Fourne
Author:
Suresh Poovathingal
Author:
Amaia Arranz-Mendiguren
Author:
Carlo Sala Frigerio
Author:
Christel Claes
Author:
Lutgarde Serneels
Author:
Tom Theys
Author:
Catherine Verfaillie
Author:
Mark Fiers
Author:
Bart De Strooper
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