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Microglia play critical roles in brain development, homeostasis, and neurological disorders. Here, we report that human microglial-like cells (iMGLs) can be differentiated from iPSCs to study their function in neurological diseases, like Alzheimer's disease (AD). We find that iMGLs develop in vitro similarly to microglia in vivo, and whole-transcriptome analysis demonstrates that they are highly similar to cultured adult and fetal human microglia. Functional assessment of iMGLs reveals that they secrete cytokines in response to inflammatory stimuli, migrate and undergo calcium transients, and robustly phagocytose CNS substrates. iMGLs were used to examine the effects of Aβ fibrils and brain-derived tau oligomers on AD-related gene expression and to interrogate mechanisms involved in synaptic pruning. Furthermore, iMGLs transplanted into transgenic mice and human brain organoids resemble microglia in vivo. Together, these findings demonstrate that iMGLs can be used to study microglial function, providing important new insight into human neurological disease.

Titel:	iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases.
Autor/in / Beteiligte Person:	Abud, EM ; Ramirez, RN ; Martinez, ES ; Healy, LM ; Nguyen, CHH ; Newman, SA ; Yeromin, AV ; Scarfone, VM ; Marsh, SE ; Fimbres, C ; Caraway, CA ; Fote, GM ; Madany, AM ; Agrawal, A ; Kayed, R ; Gylys, KH ; Cahalan, MD ; Cummings, BJ ; Antel, JP ; Mortazavi, A ; Carson, MJ ; Poon, WW ; Blurton-Jones, M
Link:	Full Text Finder (Volltext)
Zeitschrift:	Neuron, Jg. 94 (2017-04-19), Heft 2, S. 278-293.e9
Veröffentlichung:	[Cambridge, Mass. : Cell Press, c1988-, 2017
Medientyp:	academicJournal
ISSN:	1097-4199 (electronic)
DOI:	10.1016/j.neuron.2017.03.042
Schlagwort:	Amyloid beta-Protein Precursor genetics Animals Cells, Cultured Cytokines metabolism Disease Models, Animal Humans Mice Peptide Fragments metabolism Alzheimer Disease metabolism Amyloid beta-Peptides metabolism Brain metabolism Induced Pluripotent Stem Cells cytology Microglia metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Neuron] 2017 Apr 19; Vol. 94 (2), pp. 278-293.e9. MeSH Terms: Alzheimer Disease / metabolism ; Amyloid beta-Peptides / metabolism ; Brain / metabolism ; Induced Pluripotent Stem Cells / cytology ; Microglia / *metabolism ; Amyloid beta-Protein Precursor / genetics ; Animals ; Cells, Cultured ; Cytokines / metabolism ; Disease Models, Animal ; Humans ; Mice ; Peptide Fragments / metabolism References: Nat Biotechnol. 2014 Jun;32(6):554-61. (PMID: 24837661) ; Neurosci Lett. 1995 Dec 29;202(1-2):17-20. (PMID: 8787820) ; J Alzheimers Dis. 2016 Sep 6;54(2):569-84. (PMID: 27472885) ; Physiol Rev. 2011 Apr;91(2):461-553. (PMID: 21527731) ; Nat Neurosci. 2015 Nov;18(11):1584-93. (PMID: 26436904) ; Curr Opin Neurobiol. 2016 Feb;36:74-81. (PMID: 26517285) ; FASEB J. 2012 May;26(5):1946-59. (PMID: 22253473) ; Acta Neuropathol Commun. 2016 Sep 02;4(1):98. 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(PMID: 21725321) Grant Information: T32 GM008620 United States GM NIGMS NIH HHS; R01 AI121945 United States AI NIAID NIH HHS; R56 AG027465 United States AG NIA NIH HHS; P01 AG000538 United States AG NIA NIH HHS; R01 AG054025 United States AG NIA NIH HHS; P50 AG016573 United States AG NIA NIH HHS; UL1 TR001414 United States TR NCATS NIH HHS; P30 CA062203 United States CA NCI NIH HHS; P50 AG005142 United States AG NIA NIH HHS; RF1 AG048099 United States AG NIA NIH HHS Contributed Indexing: Keywords: 3D organoids; AD-GWAS; Alzheimer’s disease; Beta-amyloid; Tau; cell models of disease; induced pluripotent stem cells; microglia; mouse transplantation; neurodegenerative diseases Substance Nomenclature: 0 (Amyloid beta-Peptides) ; 0 (Amyloid beta-Protein Precursor) ; 0 (Cytokines) ; 0 (Peptide Fragments) Entry Date(s): Date Created: 20170421 Date Completed: 20170808 Latest Revision: 20220409 Update Code: 20231215 PubMed Central ID: PMC5482419

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iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases.