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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
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
1097-6256
2111-2116
Mancuso, Renzo
05786562-a993-4e37-926e-3c1fcf50b36d
Van Den Daele, Johanna
bd3e0de9-750b-407c-9c98-bfa29b50201e
Fattorelli, Nicola
bdb2f9c5-59de-47f4-b304-0b81e0ed5d58
Wolfs, Leen
cd49dd65-218b-4b13-944d-723f39233f3c
Balusu, Sriram
0af8bdbf-6fd0-4c46-966c-b89235466d87
Burton, Oliver
71c0d7be-580f-4a6f-a8a2-47a4596e02f3
Liston, Adrian
6b943804-e074-43e1-9941-768004e95042
Sierksma, Annerieke
c0aeba1c-f01a-462e-8819-b714cac13f35
Fourne, Yannick
93fd94f4-60f5-44be-9fd9-423a79c2c01e
Poovathingal, Suresh
780f03fa-1ed4-4e45-be7d-c5087d592956
Arranz-Mendiguren, Amaia
9db19e6f-6f31-40c7-9deb-d1516fccc348
Sala Frigerio, Carlo
ce10cc6f-db95-4c2a-af60-134ac468b829
Claes, Christel
a2f9e9c2-83b8-404f-8e31-29d1b5311e97
Serneels, Lutgarde
54c6d6ff-837f-4686-a4fa-37dda69f76d2
Theys, Tom
d442e1fc-5ec7-4aaa-8b01-951fd579793d
Perry, V Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
Verfaillie, Catherine
fe5eae96-27e6-4024-a6f5-9ad0cd56b41b
Fiers, Mark
36374677-3e36-4eb6-91da-6c4a3b2ad3ad
De Strooper, Bart
1df9ea7c-2c32-4598-912d-39feeb77368f
Mancuso, Renzo
05786562-a993-4e37-926e-3c1fcf50b36d
Van Den Daele, Johanna
bd3e0de9-750b-407c-9c98-bfa29b50201e
Fattorelli, Nicola
bdb2f9c5-59de-47f4-b304-0b81e0ed5d58
Wolfs, Leen
cd49dd65-218b-4b13-944d-723f39233f3c
Balusu, Sriram
0af8bdbf-6fd0-4c46-966c-b89235466d87
Burton, Oliver
71c0d7be-580f-4a6f-a8a2-47a4596e02f3
Liston, Adrian
6b943804-e074-43e1-9941-768004e95042
Sierksma, Annerieke
c0aeba1c-f01a-462e-8819-b714cac13f35
Fourne, Yannick
93fd94f4-60f5-44be-9fd9-423a79c2c01e
Poovathingal, Suresh
780f03fa-1ed4-4e45-be7d-c5087d592956
Arranz-Mendiguren, Amaia
9db19e6f-6f31-40c7-9deb-d1516fccc348
Sala Frigerio, Carlo
ce10cc6f-db95-4c2a-af60-134ac468b829
Claes, Christel
a2f9e9c2-83b8-404f-8e31-29d1b5311e97
Serneels, Lutgarde
54c6d6ff-837f-4686-a4fa-37dda69f76d2
Theys, Tom
d442e1fc-5ec7-4aaa-8b01-951fd579793d
Perry, V Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
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), 2111-2116. (doi:10.1101/562561).

Record type: Article

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.

Full text not available from this repository.

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

Catalogue record

Date deposited: 20 Mar 2020 17:30
Last modified: 14 Sep 2021 17:07

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