Microglial transcription profiles in mouse and human are driven by APOE4 and sex

Summary: Apolipoprotein E4 (APOE4) is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). APOE4 is known to affect the function of microglia, but to what extent this gene drives microglial gene expression has thus far not been examined. Using a transgenic mouse model of AD that...

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Autores principales:	V. Alexandra Moser, Michael J. Workman, Samantha J. Hurwitz, Rachel M. Lipman, Christian J. Pike, Clive N. Svendsen
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Molecular biology Biology of gender Transcriptomics Science Q
Acceso en línea:	https://doaj.org/article/fd27aedfef3942159b202a822dc10a26
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spelling	oai:doaj.org-article:fd27aedfef3942159b202a822dc10a262021-11-20T05:08:43ZMicroglial transcription profiles in mouse and human are driven by APOE4 and sex2589-004210.1016/j.isci.2021.103238https://doaj.org/article/fd27aedfef3942159b202a822dc10a262021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221012062https://doaj.org/toc/2589-0042Summary: Apolipoprotein E4 (APOE4) is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). APOE4 is known to affect the function of microglia, but to what extent this gene drives microglial gene expression has thus far not been examined. Using a transgenic mouse model of AD that expresses human APOE, we identify a unique transcriptional profile associated with APOE4 expression. We also show a sex and APOE interaction, such that both female sex and APOE4 drive expression of this gene profile. We confirm these findings in human cells, using microglia derived from induced pluripotent stem cells (iMGL). Moreover, we find that these interactions are driven in part by genes related to metal processing, and we show that zinc treatment has APOE genotype-dependent effects on iMGL. These data identify a sex- and APOE4-associated microglial transcription profile and highlight the importance of considering interactive risk factors such as sex and environmental exposures.V. Alexandra MoserMichael J. WorkmanSamantha J. HurwitzRachel M. LipmanChristian J. PikeClive N. SvendsenElsevierarticleMolecular biologyBiology of genderTranscriptomicsScienceQENiScience, Vol 24, Iss 11, Pp 103238- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Molecular biology Biology of gender Transcriptomics Science Q
spellingShingle	Molecular biology Biology of gender Transcriptomics Science Q V. Alexandra Moser Michael J. Workman Samantha J. Hurwitz Rachel M. Lipman Christian J. Pike Clive N. Svendsen Microglial transcription profiles in mouse and human are driven by APOE4 and sex
description	Summary: Apolipoprotein E4 (APOE4) is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). APOE4 is known to affect the function of microglia, but to what extent this gene drives microglial gene expression has thus far not been examined. Using a transgenic mouse model of AD that expresses human APOE, we identify a unique transcriptional profile associated with APOE4 expression. We also show a sex and APOE interaction, such that both female sex and APOE4 drive expression of this gene profile. We confirm these findings in human cells, using microglia derived from induced pluripotent stem cells (iMGL). Moreover, we find that these interactions are driven in part by genes related to metal processing, and we show that zinc treatment has APOE genotype-dependent effects on iMGL. These data identify a sex- and APOE4-associated microglial transcription profile and highlight the importance of considering interactive risk factors such as sex and environmental exposures.
format	article
author	V. Alexandra Moser Michael J. Workman Samantha J. Hurwitz Rachel M. Lipman Christian J. Pike Clive N. Svendsen
author_facet	V. Alexandra Moser Michael J. Workman Samantha J. Hurwitz Rachel M. Lipman Christian J. Pike Clive N. Svendsen
author_sort	V. Alexandra Moser
title	Microglial transcription profiles in mouse and human are driven by APOE4 and sex
title_short	Microglial transcription profiles in mouse and human are driven by APOE4 and sex
title_full	Microglial transcription profiles in mouse and human are driven by APOE4 and sex
title_fullStr	Microglial transcription profiles in mouse and human are driven by APOE4 and sex
title_full_unstemmed	Microglial transcription profiles in mouse and human are driven by APOE4 and sex
title_sort	microglial transcription profiles in mouse and human are driven by apoe4 and sex
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/fd27aedfef3942159b202a822dc10a26
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_version_	1718419578182172672

Microglial transcription profiles in mouse and human are driven by APOE4 and sex

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