cat no | io1031, io1032
ioMicroglia APOE 4/4 C112R/C112R
Human iPSC-derived Alzheimer's disease model
ioMicroglia APOE 4/4 are opti-ox deterministically programmed 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.
Benchtop benefits
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.
Quick
Rapidly maturing cells that are ready to use within 10 days post-revival, in mono- and co-cultures.
Functional
Disease model cells display key phagocytic and cytokine secretion functions.
Cells arrive ready to plate
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
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
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
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
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
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.
(LinkedValues: [{hs_name=Quantifying C5a-mediated chemotaxis in precision reprogrammed hiPSC-derived ioMicroglia, hs_id=169942560168, hs_path=quantifying-c5a-mediated-chemotaxis-in-human-ipsc-derived-microglia, button_label=null, button_link=null, type={label=Application note, value=Application note}, thumbnail={alt_text=Microglia blog email header format, width=1504, url=https://14527135.fs1.hubspotusercontent-na1.net/hubfs/14527135/Emails/Header%20images/Header%20Images%20-%20ICC%20only/Microglia%20blog%20email%20header%20format.png, height=850}, year={label=2024, value=2024}, summary=<p>bit.bio | Medicines Discovery Catapult</p>
<p>2024</p>, date_published=1717977600000, sort_date=1717977600000, tags=[{label=ioMicroglia, value=ioMicroglia}], media_contact=V1<br>2024<br>bit.bio | Medicines Discovery Catapult, listing_button_label=Download}, {hs_name=Sartorius application note - Advanced in vitro Modeling of Human iPSC-derived Neuronal Mono- and Co-cultures with Microglia, hs_id=177620758074, hs_path=sartorius-application-note-advanced-in-vitro-modeling-of-human-ipsc-derived-neuronal-mono-and-co-cultures-with-microglia, button_label=null, button_link=null, type={label=Application note, value=Application note}, thumbnail={alt_text=co culture low density progenitors compressed, width=1732, url=https://14527135.fs1.hubspotusercontent-na1.net/hubfs/14527135/Website%20content/Product%20pages/ioMicroglia/co%20culture%20low%20density%20progenitors%20compressed.png, height=970}, year={label=2024, value=2024}, summary=Trigg et al.,<br>Sartorius<br>2024, date_published=1725580800000, sort_date=1725580800000, tags=[{label=ioGlutamatergic Neurons, value=ioGlutamatergic Neurons}, {label=ioMicroglia, value=ioMicroglia}, {label=ioGlutamatergic Neurons HTT 50CAG/WT, value=ioGlutamatergic Neurons HTT 50CAG/WT}], media_contact=Trigg et al.,<br>Sartorius<br>2024, listing_button_label=Download}, {hs_name=Improving physiological relevance in neurological disease drug development, hs_id=169978477617, hs_path=improving-physiological-relevance-neurological-disease-drug-development-with-human-ipsc-derived-microglia, button_label=null, button_link=null, type={label=Case study, value=Case study}, thumbnail={alt_text=Elise Malavasi_Concept Life Sciences image, width=1800, url=https://14527135.fs1.hubspotusercontent-na1.net/hubfs/14527135/Website%20content/Resources/Case%20Studies/Concept%20Life%20Sciences_ioMicroglia%20Male/Elise%20Malavasi_Concept%20Life%20Sciences%20image.jpg, height=1199}, year={label=2024, value=2024}, summary=<p>Elise Malavasi, PhD<br>Principal Scientist<br>Concept Life Sciences</p>, date_published=1717977600000, sort_date=1717977600000, tags=[{label=ioMicroglia, value=ioMicroglia}], media_contact=V1 <br>2024 <br>bit.bio | Concept Life Sciences , listing_button_label=Download}, {hs_name=ioMicroglia, hs_id=164676247912, hs_path=microglia, button_label=View brochure, button_link=https://14527135.fs1.hubspotusercontent-na1.net/hubfs/14527135/Website%20content/Resources/Brochures/bit.bio-ioMicroglia-Male-Brochure.pdf, type={label=Brochure, value=Brochure}, thumbnail={alt_text=Microglia hero 2 resize brighten v2 compress, width=1800, url=https://14527135.fs1.hubspotusercontent-na1.net/hubfs/14527135/Website%20content/Product%20pages/ioMicroglia/Microglia%20hero%202%20resize%20brighten%20v2%20compress.png, height=1800}, year={label=2024, value=2024}, summary=bit.bio, date_published=1713312000000, sort_date=1713312000000, tags=[{label=ioMicroglia, value=ioMicroglia}, {label=Product information, value=Product information}], media_contact=null, listing_button_label=Download}, {hs_name=Rapid and consistent generation of functional microglia from reprogrammed hiPSCs to study neurodegeneration and neuroinflammation, hs_id=161961134491, hs_path=poster-rapid_and_consistent_generation_of_functional_ipsc_derived_microglia, button_label=View poster, button_link=https://14527135.fs1.hubspotusercontent-na1.net/hubfs/14527135/Website%20content/Product%20pages/ioMicroglia/bitbio-ioMicroglia_poster-V7-press_SfN%202022.pdf, type={label=Poster, value=Poster}, thumbnail={alt_text=, width=1504, url=https://14527135.fs1.hubspotusercontent-na1.net/hubfs/14527135/Emails/Header%20images/Header%20Images%20-%20ICC%20only/Microglia%20blog%20email%20header%20format.png, height=850}, year={label=2022, value=2022}, summary=<p>Raman, et al</p>
<p>bit.bio</p>
<p>2022</p>, date_published=1709251200000, sort_date=1669680000000, tags=[{label=ioGlutamatergic Neurons, value=ioGlutamatergic Neurons}, {label=ioMicroglia, value=ioMicroglia}], media_contact=null, listing_button_label=View}, {hs_name=Generation and characterisation of a panel of human iPSC-derived neurons and microglia carrying early and late onset relevant mutations for Alzheimer’s disease, hs_id=161961134495, hs_path=slas2024-ad-poster, button_label=null, button_link=null, type={label=Poster, value=Poster}, thumbnail={alt_text=, width=1800, url=https://14527135.fs1.hubspotusercontent-na1.net/hubfs/14527135/Website%20content/Product%20pages/ioMicroglia/Microglia%20hero%202%20resize%20brighten%20v2%20compress.png, height=1800}, year={label=2024, value=2024}, summary=Smith, et al. <br>bit.bio<br>2024, date_published=1711065600000, sort_date=1708300800000, tags=[{label=ioGlutamatergic Neurons, value=ioGlutamatergic Neurons}, {label=ioGABAergic Neurons, value=ioGABAergic Neurons}, {label=ioMicroglia, value=ioMicroglia}], media_contact=Smith et al. <br>bit.bio<br>2024, listing_button_label=Download}, {hs_name=CRISPR knockout screening for drug target identification and validation using CRISPR-Ready ioMicroglia, hs_id=168100039534, hs_path=slas-2024-crisprready-iomicroglia, button_label=null, button_link=null, type={label=Poster, value=Poster}, thumbnail={alt_text=bitbio-ioMicroglia_knockout-email_header-600x339, width=601, url=https://14527135.fs1.hubspotusercontent-na1.net/hubfs/14527135/Emails/Header%20images/Header%20Images%20-%20graphically%20designed/bitbio-ioMicroglia_knockout-email_header-600x339.png, height=340}, year={label=2024, value=2024}, summary=Schmidt, et al<br>bit.bio<br>2024, date_published=1716336000000, sort_date=1716336000000, tags=[{label=ioMicroglia, value=ioMicroglia}, {label=CRISPR-Ready ioCells, value=CRISPR-Ready ioCells}, {label=CRISPR-Ready ioMicroglia, value=CRISPR-Ready ioMicroglia}], media_contact=<p>Schmidt et al</p>
<p>bit.bio<br>2024</p>, listing_button_label=Download}, {hs_name=Reprogramming the stem cell for a new generation of cures, hs_id=161968263465, hs_path=reprogramming-the-stem-cell-for-a-new-generation-of-cures, button_label=Read more, button_link=https://www.ddw-online.com/reprogramming-the-stem-cell-for-a-new-generation-of-cures-1459-202004/, type={label=Publication, value=Publication}, thumbnail={alt_text=, width=2092, url=https://14527135.fs1.hubspotusercontent-na1.net/hubfs/14527135/bit.bio%20ioGlutamatergic%20Neurons%202022.jpg, height=1584}, year={label=2020, value=2020}, summary=<p>Davenport A, Frolov T & Kotter M</p>
<p><em>Drug Discovery World</em></p>
<p>2020</p>
<p> </p>
<p> </p>, date_published=1585872000000, sort_date=1597968000000, tags=[{label=ioGlutamatergic Neurons, value=ioGlutamatergic Neurons}, {label=ioSkeletal Myocytes, value=ioSkeletal Myocytes}, {label=ioGABAergic Neurons, value=ioGABAergic Neurons}, {label=ioMicroglia, value=ioMicroglia}, {label=ioSensory Neurons, value=ioSensory Neurons}, {label=ioMotor Neurons, value=ioMotor Neurons}, {label=ioAstrocytes, value=ioAstrocytes}], media_contact=<p><span>Davenport A, Frolov T & Kotter M.</span></p>
<p><em>Drug Discovery World</em></p>
<p>2020</p>
<p> </p>
<p> </p>, listing_button_label=Read more}, {hs_name=Circadian clocks in human cerebral organoids, hs_id=178051600304, hs_path=circadian-clocks-in-human-cerebral-organoids-article, button_label=Read more, button_link=https://www.biorxiv.org/content/10.1101/2024.02.20.580978v1.full, type={label=Publication, value=Publication}, thumbnail={alt_text=Hero image_CRISPR-Ready ioMicroglia, width=1422, url=https://14527135.fs1.hubspotusercontent-na1.net/hubfs/14527135/Website%20content/Product%20pages/ioMicroglia/Hero%20image_CRISPR-Ready%20ioMicroglia.png, height=1920}, year={label=2024, value=2024}, summary=<p>Rzechorzek, et al</p>
<p><em>bioRxiv</em></p>
<p>2024</p>
<p>Featuring <a href="https://www.bit.bio/platform" rel="noopener" target="_blank">opti-ox</a><sup> </sup>enabled microglia male iPS cell line and opti-ox enabled glutamatergic neurons iPS cell line</p>, date_published=1708473600000, sort_date=1708473600000, tags=[{label=ioGlutamatergic Neurons, value=ioGlutamatergic Neurons}, {label=ioMicroglia, value=ioMicroglia}], media_contact=<p>Rzechorzek, et al</p>
<p><em>bioRxiv</em></p>
<p>2024</p>
<p>Featuring <a href="https://www.bit.bio/platform" rel="noopener" target="_blank">opti-ox</a><sup> </sup>enabled microglia male iPS cell line and opti-ox enabled glutamatergic neurons iPS cell line</p>, listing_button_label=Read more}, {hs_name=Precision Cellular Reprogramming for Scalable and Consistent Human Neurodegenerative Disease Models, hs_id=161968263479, hs_path=precision-cellular-reprogramming-for-scalable-and-consistent-human-neurodegenerative-disease-models, button_label=Explore ioDisease Model Cells, button_link=https://www.bit.bio/iodisease-models, type={label=Talk, value=Talk}, thumbnail={alt_text=, width=1860, url=https://14527135.fs1.hubspotusercontent-na1.net/hubfs/14527135/Website%20content/Resources/Tech%20Nets%20online%20symposium%20header%20(1).png, height=1260}, year={label=2023, value=2023}, summary=<p>Madeleine Garrett | Field Application Specialist | bit.bio</p>, date_published=1709078400000, sort_date=1681344000000, tags=[{label=ioGlutamatergic Neurons, value=ioGlutamatergic Neurons}, {label=ioGlutamatergic Neurons HTT 50CAG/WT, value=ioGlutamatergic Neurons HTT 50CAG/WT}, {label=ioMicroglia, value=ioMicroglia}, {label=ioGlutamatergic Neurons TDP-43 M337V Het, value=ioGlutamatergic Neurons TDP-43 M337V Het}, {label=ioGlutamatergic Neurons TDP-43 M337V Hom, value=ioGlutamatergic Neurons TDP-43 M337V Hom}, {label=ioGlutamatergic Neurons MAPT P301S/WT, value=ioGlutamatergic Neurons MAPT P301S/WT}, {label=ioGlutamatergic Neurons MAPT P301S/P301S, value=ioGlutamatergic Neurons MAPT P301S/P301S}, {label=ioGlutamatergic Neurons MAPT N279K/WT, value=ioGlutamatergic Neurons MAPT N279K/WT}, {label=ioOligodendrocyte-like cells, value=ioOligodendrocyte-like cells}, {label=ioMotor Neurons, value=ioMotor Neurons}], media_contact=null, listing_button_label=Watch now}, {hs_name=ioMicroglia portfolio | Human iPSC-derived microglia | User manual, hs_id=161968263489, hs_path=microglia, button_label=null, button_link=null, type={label=User manual, value=User manual}, thumbnail={alt_text=, width=2400, url=https://14527135.fs1.hubspotusercontent-na1.net/hubfs/14527135/Website%20content/Product%20pages/ioMicroglia/bit.bio_40x%20ioMicroglia%20continuous%20culture.jpg, height=1510}, year={label=2024, value=2024}, summary=<p><span>V7</span></p>
<p><span>bit.bio</span></p>
<p><span>2024</span></p>, date_published=1709337600000, sort_date=1710374400000, tags=[{label=Product information, value=Product information}, {label=ioMicroglia, value=ioMicroglia}], media_contact=<p>V7</p>
<p>bit.bio</p>
<p>2024</p>, listing_button_label=Download}, {hs_name=Modelling human neurodegenerative diseases in research & drug discovery, hs_id=161968263520, hs_path=modelling-human-neurodegenerative-diseases-in-research-drug-discovery, button_label=Explore ioDisease Model Cells, button_link=https://www.bit.bio/iodisease-models, type={label=Webinar, value=Webinar}, thumbnail={alt_text=, width=1200, url=https://14527135.fs1.hubspotusercontent-na1.net/hubfs/14527135/BitBio2022/product-page/Colour%20webinar%20with%20it-bio%20ioGlutamatergic%20Neurons_VGLUT2(G)_MAP2(R)_Tubb3(B)_Hoechst(B)_20x_merge-comp.jpg, height=717}, year={label=2022, value=2022}, summary=<p><span>Dr Mariangela Iovino | Group Leader | Charles River</span></p>
<p><span>Dr Tony Oosterveen | Senior Scientist | bit.bio</span></p>, date_published=1707523200000, sort_date=1649116800000, tags=[{label=ioGABAergic Neurons, value=ioGABAergic Neurons}, {label=Product information, value=Product information}, {label=ioGlutamatergic Neurons HTT 50CAG/WT, value=ioGlutamatergic Neurons HTT 50CAG/WT}, {label=ioMicroglia, value=ioMicroglia}, {label=ioGlutamatergic Neurons TDP-43 M337V Het, value=ioGlutamatergic Neurons TDP-43 M337V Het}, {label=ioGlutamatergic Neurons TDP-43 M337V Hom, value=ioGlutamatergic Neurons TDP-43 M337V Hom}, {label=ioSensory Neurons, value=ioSensory Neurons}], media_contact=<p> </p>
<p> </p>, listing_button_label=Watch now}, {hs_name=Alzheimer’s Disease Pathogenesis: Emerging Role of Microglia, hs_id=161968263522, hs_path=alzheimers-disease-pathogenesis-emerging-role-of-microglia, button_label=null, button_link=null, type={label=Webinar, value=Webinar}, thumbnail={alt_text=, width=1200, url=https://14527135.fs1.hubspotusercontent-na1.net/hubfs/14527135/Emails/Webinar/Bit-bio%20Resources%20-%20ioMicroglia%20GEN%20Webinar.png, height=730}, year={label=2022, value=2022}, summary=<p>Dr Matthias Pawlowski | Head, Dementia-Sensitive Hospital | University of Münster</p>
<p><span>Dr Malathi Raman | Senior Product Manager | bit.bio</span></p>, date_published=1708214400000, sort_date=1666569600000, tags=[{label=ioMicroglia, value=ioMicroglia}, {label=ioOligodendrocyte-like cells, value=ioOligodendrocyte-like cells}], media_contact=<p> </p>
<p> </p>, listing_button_label=Watch now}, {hs_name=Rethinking Developmental Biology With Cellular Reprogramming, hs_id=161968263524, hs_path=rethinking-developmental-biology-with-cellular-reprogramming, button_label=Explore ioCells, button_link=https://www.bit.bio/discover-iocells, type={label=Webinar, value=Webinar}, thumbnail={alt_text=, width=1860, url=https://14527135.fs1.hubspotusercontent-na1.net/hubfs/14527135/Website%20content/Upcoming%20Webinars/Tech%20Nets%202023/bit.bio_ioGlutamatergic%20Neurons_20xMAP2(red)Hoescht(blue)_day12v2.png, height=1260}, year={label=2023, value=2023}, summary=<p>Mark Kotter | CEO and founder | bit.bio</p>
<p>Marius Wernig | Professor Departments of Pathology and Chemical and Systems Biology | Stanford University</p>, date_published=1709164800000, sort_date=1681776000000, tags=[{label=ioGlutamatergic Neurons, value=ioGlutamatergic Neurons}, {label=ioGABAergic Neurons, value=ioGABAergic Neurons}, {label=ioMicroglia, value=ioMicroglia}, {label=Cell therapy, value=Cell therapy}, {label=ioSensory Neurons, value=ioSensory Neurons}, {label=ioOligodendrocyte-like cells, value=ioOligodendrocyte-like cells}], media_contact=null, listing_button_label=Watch now}, {hs_name=Mastering Cell Identity In A Dish: The Power Of Cellular Reprogramming, hs_id=161968263526, hs_path=mastering-cell-identity-in-a-dish-the-power-of-cellular-reprogramming, button_label=null, button_link=null, type={label=Webinar, value=Webinar}, thumbnail={alt_text=, width=3926, url=https://14527135.fs1.hubspotusercontent-na1.net/hubfs/14527135/Website%20content/Upcoming%20Webinars/GEN%2023rd%20June%202023/io1013S-ioGlutamatergic-Neurons-PRKN-R275W-heterozygous-ICC-DAPI-MAP2.jpeg, height=1629}, year={label=2023, value=2023}, summary=<p>Prof Roger Pedersen | Adjunct Professor and Senior Research Scientist at Stanford University </p>
<p>Dr Thomas Moreau | Director of Cell Biology Research | bit.bio</p>, date_published=1709856000000, sort_date=1686700800000, tags=[{label=ioGABAergic Neurons, value=ioGABAergic Neurons}, {label=ioMicroglia, value=ioMicroglia}, {label=ioSensory Neurons, value=ioSensory Neurons}, {label=ioMotor Neurons, value=ioMotor Neurons}], media_contact=null, listing_button_label=Watch now}])
Sartorius application note - Advanced in vitro Modeling of Human iPSC-derived Neuronal Mono- and Co-cultures with Microglia
Download
Improving physiological relevance in neurological disease drug development
Download
Quantifying C5a-mediated chemotaxis in precision reprogrammed hiPSC-derived ioMicroglia
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CRISPR knockout screening for drug target identification and validation using CRISPR-Ready ioMicroglia
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.
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