cat no | io1046
ioMotor Neurons TDP-43 M337V/M337V
Human iPSC-derived ALS and FTD disease model
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Cryopreserved human iPSC-derived cells powered by opti-ox, that are ready for experiments in days
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Engineered to enable investigations into the impact of mutant TDP-43 protein on neurodegenerative disease
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Clump free, highly-pure motor neurons, that form functional neuronal networks in co-culture with astrocytes
Human iPSC-derived ALS and FTD disease model
ioMotor Neurons TDP-43 M337V/M337V form a homogenous neuronal network by day 4
ioMotor Neurons TDP-43 M337V/M337V rapidly acquire a motor neuronal phenotype, forming homogenous neuronal networks, without clumping of cells. Compared to the genetically matched wild type control, ioMotor Neurons. Day 1 to 11 post thawing; 100X magnification.
ioMotor Neurons TDP‑43 M337V/M337V express motor neuron-specific markers with protein expression highly reminiscent to the genetically matched control
Immunofluorescent staining on post-revival day 11 demonstrates similar homogenous expression of pan-neuronal protein TUBB3, motor neuron specific marker ISL2 and the cholinergic marker VAChT in ioMotor Neurons TDP‑43 M337V/M337V compared to the genetically matched control, ioMotor Neurons.
ioMotor Neurons TDP‑43 M337V/M337V express motor neuron-specific markers with protein expression highly reminiscent to the genetically matched control
Immunofluorescent staining on post-revival day 11 demonstrates similar homogenous expression of pan-neuronal protein MAP2, motor neuron specific marker HB9 and the cholinergic marker VAChT in ioMotor Neurons TDP‑43 M337V/M337V compared to the genetically matched control, ioMotor Neurons.
ioMotor Neurons TDP‑43 M337V/M337V demonstrate gene expression of neuronal-specific and motor neuron-specific markers following deterministic programming
Gene expression analysis demonstrates that ioMotor Neurons TDP‑43 M337V/M337V and the genetically matched control (WT) lack the expression of pluripotency makers (NANOG and OCT4), at day 11, whilst robustly expressing pan-neuronal (MAP2), cholinergic (CHAT and VACHT) and motor neuron-specific (MNX1 and ISL2) markers. 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.
View the step-by-step RNA extraction and RT-qPCR protocol used to generate this data
Disease-related TARDBP is expressed in ioMotor Neurons TDP‑43 M337V/M337V following deterministic programming
Gene expression analysis demonstrates that ioMotor Neurons TDP‑43 M337V/M337V and the genetically matched 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.
Co-culture of ioMotor Neurons and ioSkeletal Myocytes
High resolution confocal imaging of ioSkeletal Myocytes (io1002) and ioMotor Neurons wild-type co-culture. Staining with alpha-bungarotoxin (yellow) highlights acetylcholine receptor expression on co-cultured ioSkeletal Myocytes. Desmin (cyan) and microtubule-associated protein 2 (red) define ioSkeletal Myocytes and ioMotor Neurons respectively. Co-culture imaged at day 30, 40X magnification.
Download the step-by-step protocol for culturing ioSkeletal Myocytes and ioMotor Neurons.
Identification of splice variants in ioGlutamatergic Neurons and ioMotor Neurons carrying the TDP-43 M337V mutation
To discover neuronal sub-type-specific TDP-43 transcript targets, we used bulk RNA-sequencing to identify alternatively spliced transcripts in ioMotor Neurons and ioGlutamatergic Neurons carrying a heterozygous or homozygous TDP-43 M337V mutation versus wild-type controls. Wild-type and mutant cells were cultured for 30 days in triplicates. RNA samples were collected at day 11, 21 and 30.
Venn diagram comparing the alternatively spliced transcripts at days 21 and 30 that are unique to and shared between ioMotor Neurons and ioGlutamatergic Neurons TDP-43 M337V het and hom genotypes, compared to their respective wild-type controls. Several targets were validated by RT-qPCR analysis, including DPP6, PKIB and PRUNE2. The genes highlighted in bold have previously been associated with FTD/ALS or have been found to be differentially spliced in samples from ALS patients.
Schematic representation of the DPP6 splice events occurring in wild-type and TDP-43 mutant ioGlutamatergic Neurons and validation by RT-qPCR
A. UCSC genome browser representation of the human DPP6 locus showing the different splice events (black rectangles) in ioGlutamatergic Neurons. Bulk RNA-seq data showed that splice variant 2 is detected more frequently in day 30 ioGlutamatergic Neurons TDP-43 M337V/M337V mutants while splice variant 1 is more abundant in wild-type control neurons. The curated RefSeq annotations of DPP6 are indicated by the blue lines. The TDP-43 track (red) shows an iCLIP data set (Halleger et al., 2021) intersecting TDP-43 binding sites with the DPP6 transcripts.
B. Graphs showing RT-qPCR analysis of day 30 (D30) ioGlutamatergic Neurons (GN) wild type (WT), TDP-43 M337V/WT (HET) and TDP-43 M337V/M337V (HOM) samples indicated respectively in grey, yellow and orange.
Alternatively spliced genes discovered by bulk RNA-seq in the TDP-43 mutant ioGlutamatergic Neurons and ioMotor Neurons were confirmed by RT-qPCR assays.
View the scientific poster presented at Society of Neuroscience 2025
Do more with every vial
The seeding density of our human iPSC-derived ioMotor Neurons and related disease models has been optimised and validated to a recommended seeding density of 30,000 cells/cm². This means scientists can do more with every vial and expand experimental design within budget without losing out on quality. Resulting in more experimental conditions, more repeats, and more confidence in the data. 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.
Vial limit exceeded
A maximum number of 20 vials applies. If you would like to order more than 20 vials, please contact us at orders@bit.bio.
