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Hallmarks of Alzheimer's Disease in Stem-Cell-Derived Human Neurons Transplanted into Mouse Brain.

Neuron | 2017

Human pluripotent stem cells (PSCs) provide a unique entry to study species-specific aspects of human disorders such as Alzheimer's disease (AD). However, in vitro culture of neurons deprives them of their natural environment. Here we transplanted human PSC-derived cortical neuronal precursors into the brain of a murine AD model. Human neurons differentiate and integrate into the brain, express 3R/4R Tau splice forms, show abnormal phosphorylation and conformational Tau changes, and undergo neurodegeneration. Remarkably, cell death was dissociated from tangle formation in this natural 3D model of AD. Using genome-wide expression analysis, we observed upregulation of genes involved in myelination and downregulation of genes related to memory and cognition, synaptic transmission, and neuron projection. This novel chimeric model for AD displays human-specific pathological features and allows the analysis of different genetic backgrounds and mutations during the course of the disease.

Pubmed ID: 28238547 RIS Download

Mesh terms: Alzheimer Disease | Animals | Brain | Cell Death | Cell Differentiation | Humans | Mice | Neurites | Neurons | Phosphorylation | Pluripotent Stem Cells | tau Proteins

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STAR (tool)

RRID:SCR_015899

Software performing alignment of high-throughput RNA-seq data. STAR is based on a previously undescribed RNA-seq alignment algorithm that uses sequential maximum mappable seed search in uncompressed suffix arrays followed by seed clustering and stitching procedure.

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Subread (tool)

RRID:SCR_009803

A toolkit for processing next-gen sequencing data. These programs were also implemented in Bioconductor R package Rsubread.

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Goat anti-Rabbit IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor 568 (antibody)

RRID:AB_143157

This polyclonal antibody targets Rabbit IgG (H+L) Cross-Adsorbed

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Polyclonal Rabbit Anti-Human Tau antibody (antibody)

RRID:AB_10013724

This polyclonal antibody targets Tau

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Monoclonal Anti-MAP2 antibody produced in mouse (antibody)

RRID:AB_477256

This monoclonal antibody targets MAP2 antibody produced in mouse

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Anti Iba1, Rabbit antibody (antibody)

RRID:AB_839504

This polyclonal antibody targets Iba1

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Purified anti-Tubulin ? 3 (TUBB3) antibody (antibody)

RRID:AB_2313773

This monoclonal antibody targets Tubulin beta 3 (TUBB3)

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NCAM (ERIC 1) antibody (antibody)

RRID:AB_627128

This monoclonal antibody targets NCAM (ERIC 1)

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Brn-2 (C-20) antibody (antibody)

RRID:AB_2167385

This polyclonal antibody targets Brn-2 (C-20)

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Rabbit Anti-Tubulin, beta, Class III, Neuronal Polyclonal Antibody, Unconjugated (antibody)

RRID:AB_291637

This polyclonal antibody targets Tubulin, beta, Class III, Neuronal

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Goat anti-Mouse IgG (H+L) Secondary Antibody, DyLight 650 (antibody)

RRID:AB_10942301

This polyclonal antibody targets Mouse IgG (H+L)

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Anti-Beta III Tubulin antibody (antibody)

RRID:AB_570918

This unknown targets Beta III Tubulin

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Anti-Synaptophysin 1 antibody (antibody)

RRID:AB_887905

This polyclonal antibody targets Synaptophysin 1

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Ctip2 antibody [25B6] - ChIP Grade (antibody)

RRID:AB_2064130

This monoclonal antibody targets Bcl11b

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Anti-Tau (3-repeat isoform RD3), clone 8E6/C11 antibody (antibody)

RRID:AB_310013

This monoclonal antibody targets Tau (3-repeat isoform RD3) clone 8E6/C11

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TBR1 antibody (antibody)

RRID:AB_2200219

This polyclonal antibody targets Tbr1

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Anti-GFP antibody (antibody)

RRID:AB_300798

This polyclonal antibody targets GFP

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Anti-Tau (4-repeat isoform RD4), clone 1E1/A6 antibody (antibody)

RRID:AB_310014

This monoclonal antibody targets Tau (4-repeat isoform RD4) clone 1E1/A6

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Goat anti-Rabbit IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor 647 (antibody)

RRID:AB_2535813

This polyclonal antibody targets Rabbit IgG (H+L) Highly Cross-Adsorbed

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Goat anti-Mouse IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor 546 (antibody)

RRID:AB_2534089

This polyclonal antibody targets Mouse IgG (H+L) Highly Cross-Adsorbed

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Anti-Synaptophysin 1 antibody (antibody)

RRID:AB_887824

This monoclonal antibody targets Synaptophysin 1

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PSD-95 antibody (antibody)

RRID:AB_397861

This monoclonal antibody targets PSD-95

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Anti-NeuN antibody (antibody)

RRID:AB_2298772

This monoclonal antibody targets NeuN

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Anti-Homer 1 antibody (antibody)

RRID:AB_887730

This polyclonal antibody targets Homer 1

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Rabbit Anti-Green Fluorescent Protein (GFP) Polyclonal Antibody, Unconjugated (antibody)

RRID:AB_221570

This polyclonal antibody targets Green Fluorescent Protein (GFP)

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MAP-2 (H-300) antibody (antibody)

RRID:AB_2250101

This polyclonal antibody targets MAP2

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SATB2 antibody (antibody)

RRID:AB_2301417

This polyclonal antibody targets Mouse SATB2

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Anti-Nuclei, clone 235-1 antibody (antibody)

RRID:AB_94090

This monoclonal antibody targets Nuclei

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Anti-GFAP antibody (antibody)

RRID:AB_10641162

This polyclonal antibody targets GFAP

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FOXG1 antibody - ChIP Grade (antibody)

RRID:AB_732415

This polyclonal antibody targets FOXG1 antibody - ChIP Grade

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