ArticleNeuron2019
Development of a Chimeric Model to Study and Manipulate Human Microglia In Vivo.
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Article in Neuron, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 245 papers.
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245citing papers in PubMed
19.4field-weighted citation impact, top 1% of its field
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Who cites it
245 citing papers in PubMed, 375 citations in OpenAlex.
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- Impaired lipoprotein secretion by APOE4 leads to lysosomal and mitochondrial dysfunction in human microglia.bioRxiv : the preprint server for biology · 2026Article
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185 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 4 institutions in 2 countries.
Jonathan HasselmannDepartment of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92696, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92696, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92696, USA.
Morgan A CoburnDepartment of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92696, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92696, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92696, USA.
Whitney EnglandDepartment of Pharmaceutical Sciences, University of California, Irvine, Irvine, CA 92697, USA.
Dario X Figueroa VelezDepartment of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92696, USA.
Sepideh Kiani ShabestariSue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92696, USA.
Christina H TuSue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92696, USA.
Amanda McQuadeDepartment of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92696, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92696, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92696, USA.
Mahshad KolahdouzanNeuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A 2B4, Canada.
Karla EcheverriaSue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92696, USA.
Christel ClaesSue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92696, USA.
Taylor NakayamaDepartment of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92696, USA.
Ricardo AzevedoDepartment of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92696, USA.
Nicole G CoufalDepartment of Pediatrics, University of California, San Diego, San Diego, CA 92093, USA.
Claudia Z HanDepartment of Cellular and Molecular Medicine, University of California, San Diego, San Diego, CA 92093, USA.
Brian J CummingsSue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92696, USA.
Hayk DavtyanSue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92696, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92696, USA.
Christopher K GlassDepartment of Cellular and Molecular Medicine, University of California, San Diego, San Diego, CA 92093, USA; Department of Medicine, University of California, San Diego, San Diego, CA 92093-0651, USA.
Luke M HealyNeuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A 2B4, Canada.
Sunil P GandhiDepartment of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92696, USA; Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, CA 92697, USA.
Robert C SpitaleDepartment of Pharmaceutical Sciences, University of California, Irvine, Irvine, CA 92697, USA; Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, CA 92697, USA.
Mathew Blurton-JonesDepartment of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92696, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92696, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92696, USA; Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: mblurton@uci.edu.
University of California, Irvine · USUniversity of California, San Diego · USMcGill University · CAMontreal Neurological Institute and Hospital · CA
Funding
Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Joel E Milam · 1994 to 2026
$57.9MUC Irvine Alzheimer's Disease Research Center Induced Pluripotent Stem Cell CoreP50AG016573 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 2000 to 2019
$37.0MTraining in the Neurobiology of Aging and Alzheimers DiseaseT32AG000096 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI VIVEK SWARUP, Craig E Stark · 1985 to 2026
$9.6MMEDICAL SCIENTIST TRAINING PROGRAMT32GM008620 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI GOLDIN, ALAN L · 1999 to 2023
$8.1MMechanisms controlling human microglia gene expressionR01NS096170 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLASS, CHRISTOPHER K · 2016 to 2025
$4.3MTraining Program in Stem Cell Translational Medicine for Neurological DisordersT32NS082174 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI PETER John DONOVAN, Leslie Michels Thompson · 2013 to 2026
$3.3MUsing human iPSC derived microglia and chimeric models to examine the role of PLCG2 in Alzheimers diseaseR01AG061895 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI DAVTYAN, HAYK · 2018 to 2022
$2.9MExamining the role of adaptive immunity in Alzheimer's Disease pathogenesisRF1AG055524 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BLURTON-JONES, MATHEW MARK · 2017 to 2017
$2.7MCracking the RNA Localization CodeDP2GM119164 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI SPITALE, ROBERT C · 2015 to 2015
$2.2MA novel platform for the investigation of human microgliaRF1DA048813 · NIDA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BLURTON-JONES, MATHEW MARK, GANDHI, SUNIL · 2019 to 2021
$2.1MManipulating DNA repair enzymes to examine the interactions between aging and Alzheimers disease with iPSC-derived microgliaR01AG056303 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BLURTON-JONES, MATHEW MARK · 2017 to 2021
$1.9MThe role of TREM2 in human microglial function and Alzheimer disease pathogenesisRF1AG048099 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BLURTON-JONES, MATHEW MARK · 2014 to 2014
$1.9MNCI NIH HHS P30 CA062203NCRR NIH HHS S10 RR025496NEI NIH HHS F30 EY029596NEI NIH HHS F31 EY028046NEI NIH HHS R01 EY028212NIA NIH HHS P50 AG016573NIA NIH HHS R01 AG056303NIA NIH HHS R01 AG061895NIA NIH HHS RF1 AG048099NIA NIH HHS RF1 AG055524NIA NIH HHS T32 AG000096NIDA NIH HHS RF1 DA048813NIGMS NIH HHS DP2 GM119164NIGMS NIH HHS T32 GM008620NIH HHS S10 OD010794NIH HHS S10 OD021718NINDS NIH HHS K08 NS109200NINDS NIH HHS R01 NS096170NINDS NIH HHS T32 NS082174
Abstract
iPSC-derived microglia offer a powerful tool to study microglial homeostasis and disease-associated inflammatory responses. Yet, microglia are highly sensitive to their environment, exhibiting transcriptomic deficiencies when kept in isolation from the brain. Furthermore, species-specific genetic variations demonstrate that rodent microglia fail to fully recapitulate the human condition. To address this, we developed an approach to study human microglia within a surrogate brain environment. Transplantation of iPSC-derived hematopoietic-progenitors into the postnatal brain of humanized, immune-deficient mice results in context-dependent differentiation into microglia and other CNS macrophages, acquisition of an ex vivo human microglial gene signature, and responsiveness to both acute and chronic insults. Most notably, transplanted microglia exhibit robust transcriptional responses to Aβ-plaques that only partially overlap with that of murine microglia, revealing new, human-specific Aβ-responsive genes. We therefore have demonstrated that this chimeric model provides a powerful new system to examine the in vivo function of patient-derived and genetically modified microglia.
Indexed as
Cell DifferentiationGene ExpressionTransplantation ChimeraAlzheimer DiseaseAmyloid beta-PeptidesAnimalsBrainDisease Models, AnimalGranulocyte-Macrophage Colony-Stimulating FactorHematopoietic Stem Cell TransplantationHumansInduced Pluripotent Stem CellsMacrophage Colony-Stimulating FactorMiceMice, TransgenicMicrogliaAmyloid beta-PeptidesCSF1 protein, humanCSF2 protein, humanGranulocyte-Macrophage Colony-Stimulating FactorMacrophage Colony-Stimulating FactorThrombopoietinAlzheimer’s diseasebeta-amyloidchimerahematopoietichumanizedmicroglianeurodegenerationpluripotentstem cellsTREM-2
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.