TDP-43 M337VWT ICC Overlay catalog hero

cat no | ioEA1006

ioGlutamatergic Neurons
TDP‑43 M337V/WT

Human iPSC-derived ALS and FTD disease model

A rapidly maturing, consistent and scalable isogenic system to study amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

ioGlutamatergic Neurons TDP‑43 M337V/WT are opti‑ox™ precision reprogrammed glutamatergic neurons carrying a genetically engineered heterozygous M337V mutation in the TARDBP gene, encoding TAR DNA binding protein 43 (TDP‑43). 

 

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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.

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Benchtop benefits

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Make True Comparisons

Pair the ioDisease Model Cells with the genetically matched wild-type ioGlutamatergic Neurons to investigate the impact of mutant TDP‑43 protein on disease progression.

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Scalable

Industrial scale quantities are available with industry-leading seeding densities, and at a price point that allows the cells to be used from research to high throughput screening.

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Quick

The disease model cells and isogenic control are experiment ready as early as 2 days post revival, and form structural neuronal networks at 11 days.

Technical data

Highly characterised and defined

ioGlutamatergic Neurons TDP‑43 M337V/WT express neuron-specific markers with protein expression highly reminiscent to the isogenic control

ioGlutamatergic_neurons-TDP43-M337V-WT-ICC-VGLUT2

Immunofluorescent staining on post-revival day 11 demonstrates similar homogenous expression of pan-neuronal proteins MAP2 and TUBB3 (upper panel) and glutamatergic neuron-specific transporter VGLUT2 (lower panel) in ioGlutamatergic Neurons TDP‑43 M337V/WT compared to the isogenic control. 100X magnification.

ioGlutamatergic Neurons TDP‑43 M337V/WT form structural neuronal networks by day 11

ioGlutamatergic_neurons-TDP43-M337V-WT-Morphology

ioGlutamatergic Neurons TDP‑43 M337V/WT mature rapidly and form structural neuronal networks over 11 days when compared to the isogenic control. Day 1 to 11 post-thawing; 100X magnification.

ioGlutamatergic Neurons TDP‑43 M337V/WT demonstrate gene expression of neuronal-specific and glutamatergic-specific markers following reprogramming

ioGlutamatergic_neurons-TDP43-M337V-WT-rt-qPCR
Gene expression analysis demonstrates that ioGlutamatergic Neurons TDP‑43 M337V/WT and the isogenic control (WT) lack the expression of pluripotency makers (NANOG and OCT4), at day 11, whilst robustly expressing pan-neuronal (TUBB3 and SYP) and glutamatergic-specific (VGLUT1 and VGLUT2) markers, and the glutamate receptor GRIA4. Gene expression levels were assessed by RT-qPCR (data expressed relative to the parental hiPSC control (iPSC Control), normalised to HMBS). Data represents day 11 post-revival samples.

Disease-related TARDBP is expressed in ioGlutamatergic Neurons TDP‑43 M337V/WT following reprogramming

ioGlutamatergic_neurons-TDP43-M337V-WT-rt-qPCR-TDP43
Gene expression analysis demonstrates that ioGlutamatergic Neurons TDP‑43 M337V/WT and the isogenic control (WT) express the TARDBP gene encoding TDP‑43. Gene expression levels were assessed by RT-qPCR (data expressed relative to the parental hiPSC control (iPSC Control), normalised to HMBS). Data represents day 11 post-revival samples.

Disease-related phenotype

Differences in neuronal activity between disease models and control cells by MEA analysis indicates the potential of the panel as a relevant translational in vitro drug discovery model for ALS and FTD
ioGlutamatergic-Neurons-TDP-43-M337V-MEA-analysis-CRL

Reduced neuronal activity was measured in ioGlutamatergic Neurons TDP-43 M337V/M337V compared to ioGlutamatergic Neurons TDP-43 M337V/WT and the isogenic control, ioGlutamatergic Neurons. Microelectrode array (MEA) chips were spotted with 100K (~900K cells/cm2) ioGlutamatergic Neurons (WT), TDP-43 M337V/WT (C20), or TDP-43 M337V/M337V (C1), along with 20K (~180K cells/cm2) human iPSC-derived astrocytes.  Brightfield at 26 DIV (A, left),  cells show good coverage of electrodes and produce clear burst and network burst activity as seen in the raster plot of activity (A, right). In the raster plot, each dash indicates a firing event, blue indicates a single electrode burst and the pink box indicates a network burst event. Quantification of raster plots over the course of culture shows that ioGlutamatergic Neurons TDP-43 M337V/M337V have a lower weighted mean firing rate, and network burst frequency than WT and ioGlutamatergic Neurons TDP-43 M337V/WT (B). No clear difference is noted between WT and TDP-43 M337V/WT. Error bars indicate SEM, n=14 technical repeats. Data courtesy of Charles River Laboratories.

Cells arrive ready to plate

ioGlutamatergic_neurons-TDP43-M337V-WT-timeline-1

ioGlutamatergic Neurons TDP‑43 M337V/WT 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: Induction, which is carried out at bit.bio (Phase 0), Stabilisation for 4 days (Phase 1), and Maintenance (Phase 2) during which the ioGlutamatergic Neurons TDP‑43 M337V/WT mature. Phases 1 and 2 after revival of cells are carried out at the customer site.

Industry leading seeding density

Do more with every vial
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ioGlutamatergic Neurons TDP‑43 M337V/WT are compatible with plates ranging from 6 to 384 wells and are available in two vial sizes, tailored to suit your experimental needs with minimal waste.

The recommended seeding density is 30,000 cells/cm2, compared to up to 500,000 cells/cm2 for other available products on the market.

One small vial can plate a minimum of 0.7 x 24-well plate, 1 x 96-well plate, or 1.5 x 384-well plate. One Large vial can plate a minimum of 3.6 x 24-well plate, 5.4 x 96-well plate, or 7.75 x 384-well plates.

Product information

Starting material

Human iPSC line

Karyotype

Normal (46, XY)

Seeding compatibility

6, 12, 24, 48, 96 & 384 well plates

Shipping info

Dry ice

Donor

Caucasian adult male (skin fibroblast)

Vial size

Small: >1 x 10 viable cells
Large: >5 x 10 viable cells

Quality control

Sterility, protein expression (ICC), genotype (Sanger seq) and gene expression (RT-qPCR)

Product use

These cells are for research use only

Differentiation method

opti-ox cellular reprogramming

Recommended seeding density

30,000 cells/cm2

User storage

LN2 or -150°C

Format

Cryopreserved cells

Applications

FTD and ALS research
Drug discovery and development
Disease modelling
High-throughput screening
Electrophysiological assays (MEA)
Co-culture studies

Genetic modification

Heterozygous M337V missense mutation in the TARDBP gene

Product resources

Axion-CRL-bitbio app note Q4 2023 Application note
Axion-CRL-bitbio app note Q4 2023
V1
2023
bit.bio | Axion BioSystems | Charles River Laboratories
Download
Modelling neurodegeneration: Human isogenic system to study FTD & ALS Poster
Modelling neurodegeneration: Human isogenic system to study FTD & ALS

Oosterveen, et al

bit.bio & Charles River Laboratories

2023

Download
Precision Cellular Reprogramming for Scalable and Consistent Human Neurodegenerative Disease Models Talk
Precision Cellular Reprogramming for Scalable and Consistent Human Neurodegenerative Disease Models

Madeleine Garrett | Field Application Specialist | bit.bio

Watch now
Genotype and phenotype validation of an isogenic human iPSC-derived neuronal model of Huntington’s Disease Poster
Genotype and phenotype validation of an isogenic human iPSC-derived neuronal model of Huntington’s Disease

Oosterveen et al

bit.bio

2022

Download
Validation of ALS-relevant phenotypes in precision reprogrammed iPSC-derived glutamatergic Neurons containing a TDP-43 M337V mutation. Poster
Validation of ALS-relevant phenotypes in precision reprogrammed iPSC-derived glutamatergic Neurons containing a TDP-43 M337V mutation.

Ritsma, et al

Charles River Laboratories & bit.bio

2022

Download

Addressing current challenges of in vitro cell models 

Read this blog to find out how experts from across academia and industry are approaching the challenges of reproducibility of in vitro cell models as well as potential solutions.

bit-bio_Addressing the challenges of cell models_Blog_Image1200x755

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Wild type and isogenic disease model cells: a true comparison.

Further your disease research by pairing our wild type Cells with isogenic disease models.

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Related pages

Discover ioCells Learn about our range of human iPSC-derived cells for research and drug discovery
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