ioMicroglia APOE4 Hom Hero croppped compressed

cat no | io1031, io1032

ioMicroglia APOE 4/4 C112R/C112R

Human iPSC-derived Alzheimer's disease model

ioMicroglia APOE 4/4 are opti-ox precision reprogrammed microglia carrying a genetically engineered homozygous C112R mutation in the APOE gene, converting the wild-type APOE3 allele to APOE4, encoding the apolipoprotein E4. The APOE4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). 

These cells offer a functional, rapidly maturing, and disease relevant system to study the role of APOE4 in late-onset AD, alongside a genetically matched wild-type control.

Place your order

Confidently investigate your phenotype of interest across multiple clones with our disease model clone panel. Detailed characterisation data (below) and bulk RNA sequencing data (upon request) help you select specific clones if required.

per vial

Benchtop benefits

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Making True Comparisons

Pair the ioDisease Model Cells with the genetically matched wild-type ioMicroglia to directly investigate the effect of APOE4 on late-onset AD.

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Quick

Rapidly maturing cells that are ready to use within 10 days post-revival, in mono- and co-cultures.

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Functional

Disease model cells display key phagocytic and cytokine secretion functions.

Technical data

Cells arrive ready to plate

bit.bio_ioMicroglia_timeline_horizontal_withoutdox

ioMicroglia APOE 4/4 are delivered in a cryopreserved format and are programmed to rapidly mature upon revival in the recommended   media. The protocol for the generation of these cells is a three-phase process: an Induction phase that is carried out at bit.bio, Phase 1: Stabilisation for 24 hours, Phase 2: Maturation for a further 9 days, Phase 3: the Maintenance phase. Cells are ready to use from day 10.

Highly characterised and defined

Disease model cells express key microglia markers comparably to the genetically matched wild-type control

ioMicroglia APOE4 Hom P2RY12 ICC Panel_FINAL3
ioMicroglia APOE4 Hom IBA1 ICC Panel_FINAL2 compressed
Immunofluorescent staining on day 10 post-revival demonstrates similar homogenous expression of microglia markers IBA1 and P2RY12 and ramified morphology in both disease model clones compared to the genetically matched wild-type (WT) control. 100X magnification.
Disease model cells show expected ramified morphology by day 10
ioMicroglia APOE4 Hom Morphology Panel FINAL2 compressed

Both disease model clones mature rapidly and key ramified morphology can be identified by day 4 and continues through to day 10, similarly to the WT control. Day 1 to 10 post-thawing; 100x magnification.

Key phagocytic function

Disease model cells show a reduced proportion of phagocytosis of E. coli particles compared to the genetically matched wild-type control
ioMicroglia APOE4 Hom phago prop ecoli graph FINAL

Phagocytosis was analysed at day 10 post-revival after incubation with 1 µg/0.33 cm2 pHrodo RED labelled E. coli particles for 24 hours +/- cytochalasin D control. The graph displays the proportion of cells phagocytosing E. coli particles over 24 hours and shows that both disease model clones display a reduced proportion of phagocytosis compared to the WT control. Images were acquired every 30 mins on the Incucyte® looking at red fluorescence and phase contrast. Three technical replicates were performed experiment. 

Disease model cells show a reduced degree of phagocytosis of E. coli particles compared to the genetically matched wild-type control
ioMicroglia APOE4 Hom phago intensity ecoli graph FINAL

Phagocytosis was analysed at day 10 post-revival after incubation with 1 µg/0.33 cm2 pHrodo RED labelled E. coli particles for 24 hours +/- cytochalasin D control. The graph displays the fluorescence intensity per cell displaying degree of phagocytosis per cell and shows that both disease model clones display a reduced degree of phagocytosis per cell compared to the WT control. Images were acquired every 30 mins on the Incucyte® looking at red fluorescence and phase contrast. Three technical replicates were performed experiment. 

Key cytokine secretion function

Disease model cells display reduced secretion of  pro-inflammatory cytokines upon activation compared to the genetically matched wild-type control
ioMicroglia APOE4 Hom cytokine graphs FINAL

Cytokine secretion was analysed at day 10 post-revival after stimulation with LPS 100 ng/ml and IFNɣ 20 ng/ml for 24 hours. This revealed that both disease model clones secrete the predominantly pro-inflammatory cytokines, IL-6, IL-8, IL-10, IL-12p70, IL-1β, and TNF⍺ at a lower-level compared to the WT control. Supernatants were harvested and analysed using MSD V-plex Proinflammatory Kit. Three technical replicates were performed experiment. 

Product information

Starting material

Human iPSC line

Seeding compatibility

6, 12, 24, 96 & 384 well plates

Shipping info

Dry ice

Donor

Caucasian adult male (skin fibroblast)

Vial size

Small: >1.5 x 10⁶ viable cells

Quality control

Sterility, protein expression (ICC), functional phagocytosis and cytokine secretion assays

Differentiation method

opti-ox cellular reprogramming

Recommended seeding density

37,000 to 39,500 cells/cm²

User storage

LN2 or -150°C

Format

Cryopreserved cells

Product use

ioCells are for research use only

Genetic modification

Homozygous C112R mutation in the APOE gene

Applications

Alzheimer's disease modelling
Drug discovery and development
Neuroinflammation modelling
Phagocytosis assays
Cytokine response assays
Co-culture studies

Available clones

io1031S: ioMicroglia APOE 4/4 C112R/C112R (CL83)
io1032S: ioMicroglia APOE 4/4 C112R/C112R (CL69)

Product resources

Improving physiological relevance in neurological disease drug development Case study
Improving physiological relevance in neurological disease drug development

Elise Malavasi, PhD
Principal Scientist
Concept Life Sciences

Download
Quantifying C5a-mediated chemotaxis in precision reprogrammed hiPSC-derived ioMicroglia Application note
Quantifying C5a-mediated chemotaxis in precision reprogrammed hiPSC-derived ioMicroglia

bit.bio | Medicines Discovery Catapult

2024

Download
CRISPR knockout screening for drug target identification and validation using CRISPR-Ready ioMicroglia Poster
CRISPR knockout screening for drug target identification and validation using CRISPR-Ready ioMicroglia
Byrne et al. 
bit.bio
2024
Download
ioMicroglia Brochure
ioMicroglia
bit.bio
Download

Alzheimer’s Disease Pathogenesis - Emerging Role of Microglia

In this GEN webinar, hear from our distinguished expert, Dr Matthias Pawlowski, and learn about the emerging role of microglia in the pathogenesis of Alzheimer’s disease and their potential as a therapeutic target to treat this disease effectively.

5C_ioMicrogliaConfocal image

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Resources Explore our latest scientific insights, webinars, blogs and videos
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