TDP-43 M337VWT ICC Overlay copy

cat no | ioEA1005

ioGlutamatergic Neurons
TDP‑43 M337V/M337V

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/M337V are opti‑ox deterministically programmed glutamatergic neurons carrying a genetically engineered homozygous M337V mutation in the TARDBP gene, encoding TAR DNA binding protein 43 (TDP‑43).

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

For academic discounts, sample requests or bulk pricing inquiries, contact us

Benchtop benefits

phenotype_0

Disease-related phenotype

MEA analysis detects lower weighted mean firing rate and network burst frequency compared to the wild‑type control.

defined_0

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.

quick_0

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/M337V express neuron-specific markers with protein expression highly reminiscent to the isogenic control

ioGlutamatergic_neurons-TDP43-M337V-M337V-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/M337V compared to the isogenic control. 100X magnification.

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

ioGlutamatergic_neurons-TDP43-M337V-M337V-Morphology

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

ioGlutamatergic_neurons-TDP43-M337V-M337V-rt-qPCR

Gene expression analysis demonstrates that ioGlutamatergic Neurons TDP‑43 M337V/M337V 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/M337V following deterministic programming

ioGlutamatergic_neurons-TDP43-M337V-M337V-rt-qPCR-TDP43

Gene expression analysis demonstrates that ioGlutamatergic Neurons TDP‑43 M337V/M337V 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

ioGlutamatergic Neurons TDP-43 M337V/M337V show reduced neuronal activity indicating their potential as a relevant translational in vitro drug discovery model for ALS and FTD

Reduced neuronal activity detected by MEA in glutamatergic neurons ALS FTD disease model cells carrying TDP-43 M337V homozygous mutation.

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_and_disease_models_timeline

ioGlutamatergic Neurons TDP‑43 M337V/M337V are delivered in a cryopreserved format and are programmed to mature rapidly upon revival in the recommended media. The protocol for the generation of these cells is a two-phase process: Phase 1, Stabilisation for 4 days; Phase 2, Maintenance, during which the neurons mature. Phases 1 and 2 after revival of cells are carried out by the customer.

Industry leading seeding density

Do more with every vial

ioGlut-WT-well_plate-2

The recommended minimum seeding density is 30,000 cells/cm2, compared to up to 250,000 cells/cm2 for other similar 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 plates. One large vial can plate a minimum of 3.6 x 24-well plates, 5.4 x 96-well plates, or 7.75 x 384-well plates. This means every vial goes further, enabling more experimental conditions and more repeats, resulting in more confidence in the data.

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 deterministic cell programming

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

Homozygous M337V missense mutation in the TARDBP gene

Product resources

Phenotypic characterisation of iPSC-derived ALS disease models by high-throughput MEA Application note
Phenotypic characterisation of iPSC-derived ALS disease models by high-throughput MEA

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

View
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

View
Modelling human neurodegenerative diseases in research & drug discovery Webinar
Modelling human neurodegenerative diseases in research & drug discovery

Dr Mariangela Iovino | Group Leader | Charles River

Dr Tony Oosterveen | Senior Scientist | bit.bio

Watch now

Cell culture hacks | human iPSC-derived glutamatergic neurons 

Read this blog on glutamatergic neuron cell culture for our top tips on careful handling, cell plating and media changes to achieve success from the outset.

bit.bio_3x2_ioGlutamatergic Neurons_MAP2_Hoescht_x20_hi.res (1)

Related products

ioGlutamatergic Neurons TDP‑43 M337V/WT ioDisease Model Cells
ioGlutamatergic Neurons TDP‑43 M337V/WT cat no. ioEA1006
Order now
ioGlutamatergic Neurons ioWild Type Cells
ioGlutamatergic Neurons cat no. io1001
Order now
CRISPR-Ready ioGlutamatergic Neurons CRISPR-Ready ioCells
CRISPR-Ready ioGlutamatergic Neurons cat no. io1090S
Order now
ioGlutamatergic Neurons MAPT N279K/WT ioDisease Model Cells
ioGlutamatergic Neurons MAPT N279K/WT cat no. io1009
Order now
ioGlutamatergic Neurons MAPT P301S/WT ioDisease Model Cells
ioGlutamatergic Neurons MAPT P301S/WT cat no. io1015
Order now
ioGlutamatergic Neurons HTT 50CAG/WT ioDisease Model Cells
ioGlutamatergic Neurons HTT 50CAG/WT cat no. ioEA1004
Order now
ioGlutamatergic Neurons PRKN R275W/WT ioDisease Model Cells
ioGlutamatergic Neurons PRKN R275W/WT cat no. io1013
Order now
ioGlutamatergic Neurons MAPT N279K/N279K ioDisease Model Cells
ioGlutamatergic Neurons MAPT N279K/N279K cat no. io1014
Order now
ioGlutamatergic Neurons MAPT P301S/P301S ioDisease Model Cells
ioGlutamatergic Neurons MAPT P301S/P301S cat no. io1008
Order now
ioGlutamatergic Neurons PRKN R275W/R275W ioDisease Model Cells
ioGlutamatergic Neurons PRKN R275W/R275W cat no. io1020
Order now

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

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

bitbio-vials-Wild_and_Disease-staggered-2500px_wide

Related pages

Discover ioCells Learn about our range of human iPSC-derived cells for research and drug discovery
Resources Explore our latest scientific insights, webinars, blogs and videos
Our platform Discover the cell coding platform that powers our ioCells