@article{b487aa97f33e42e594ca2b9eeef7ea4f,
title = "iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases",
abstract = "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.",
keywords = "3D organoids, AD-GWAS, Alzheimer's disease, Beta-amyloid, Tau, cell models of disease, induced pluripotent stem cells, microglia, mouse transplantation, neurodegenerative diseases",
author = "Abud, {Edsel M.} and Ramirez, {Ricardo N.} and Martinez, {Eric S.} and Healy, {Luke M.} and Nguyen, {Cecilia H.H.} and Newman, {Sean A.} and Yeromin, {Andriy V.} and Scarfone, {Vanessa M.} and Marsh, {Samuel E.} and Cristhian Fimbres and Caraway, {Chad A.} and Fote, {Gianna M.} and Madany, {Abdullah M.} and Anshu Agrawal and Rakez Kayed and Gylys, {Karen H.} and Cahalan, {Michael D.} and Cummings, {Brian J.} and Antel, {Jack P.} and Ali Mortazavi and Carson, {Monica J.} and Poon, {Wayne W.} and Mathew Blurton-Jones",
note = "Funding Information: This work was supported by NIH AG048099 (M.B.-J.), AG016573 (M.B.-J. and W.W.P.), AG054025 (R.K.), CIRM RT3-07893 (M.B.-J.), Alzheimer's Association BFG-14-317000 (M.B.-J.), a Stem Cell Research Center SEED grant for BORGs (B.J.C.), UC Irvine MSTP NIH T32-GM008620 (E.M.A. and G.M.F.), a Burden Fellowship (A.M.M.), and a generous gift from the Susan Scott Foundation (M.B.-J.). iPSC lines were generated by the UCI-ADRC iPS cell core funded by NIH AG016573. We thank the UCI High-Throughput Genomics Core, the Institute for Immunology, and Dr. Jennifer Atwood and Dr. Melanie Oakes. Blood donor program was supported by the NCRR and the NCATS through Grant UL1 TR001414. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = apr,
day = "19",
doi = "10.1016/j.neuron.2017.03.042",
language = "English (US)",
volume = "94",
pages = "278--293.e9",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "2",
}