iCell Motor Neurons, ALS TDP43, 01279

Disease Model

Kit Size

Catalog #: R1144
Catalog #: R1145

Cells Only

Catalog #: C1161
Catalog #: C1162
Catalog #: C1162

Motor Neurons ALS/FTD differentiated from human iPS cells, frozen

From
$2,295.00

Isogenic Control

Kit Size

Catalog #: R1051
Catalog #: R1049

Cells Only

Catalog #: C1050
Catalog #: C1048
Catalog #:

Motor Neurons ALS/FTD differentiated from human iPS cells, frozen

From
$595.00
Catalog # CPXXX

Product Overview

Tar DNA binding protein (TDP-43) is a highly conserved ribonuclear protein that accumulates as ubiquitinated inclusions in both Amyotrophic Lateral Sclerosis (ALS) and (Frontotemporal Dementia) FTD patients. TDP-43 normally shuttles between the nucleus and cytoplasm where it functions to regulate RNA splicing, stability and transport. TDP-43 neuropathology is found in most familial and sporadic ALS; therefore, understanding TDP-43 dysfunction may yield paths to therapeutic intervention.  Further TDP-43 mutations, including the M337V and Q331K variants, account for nearly 5% of familial ALS.  Therefore, understanding the pathogenic mechanism of these disease-causing mutations will increase our understanding of TDP-43 biology and identify disease-modifying treatments.

To facilitate ALS/FTD research efforts, isogenic models of ALS motor neurons were generated. CRISPR gene-editing was employed to introduce either the M337V or Q331K mutation into the parental induced pluripotent stem (iPS) cell line of our iCell Motor Neurons. These gene-edited iPS cells were fully differentiated into highly pure human cells that exhibit similar metrics to our apparently healthy iCell Motor Neurons.

Isogenic disease model iCell Motor Neurons ALS TDP43 M337V and TDP43 Q331K combined with iCell Motor Neurons provide a precision medicine-based approach that facilitates functional genomics studies, the identification of druggable pathways, and development of co-culture models to identify motor neuron phenotypes due to single base pair changes.  Together they can be used to identify altered function and disease mechanisms related to TDP-43, for drug discovery and identification of ALS/FTD therapeutic targets, and for development of neuromuscular junction disease modeling.

Components:

Need Help With This Product?

Our specialists are here to help you find the best product for your application.

Our regular business hours are 9:00am to 5:00pm Central Time (USA)

Need Help With This Product?

Our specialists are here to help you find the best product for your application.

Our regular business hours are 9:00am to 5:00pm Central Time (USA)

Performance Data

iCell Motor Neurons ALS TDP43 are a High-Purity Motor Neuron Population

Flow cytometry analysis show that iCell Motor Neurons ALS TDP43 are typically > 90% Tuj+Nestin- and ≥70% Isl1/2 at 14 days in vitro.

Figure 1: iCell Motor Neurons ALS TDP43 are a High-Purity Motor Neuron Population

Figure 2: Venn Diagram of iCell Motor Neurons ALS TDP43 Pathway Alterations

A Comprehensive Validation of iCell Motor Neurons ALS TDP43 RNA-seq Analysis Identified Potential Pathways with Druggable Targets.

RNA-seq analysis of iCell Motor Neurons comparing the TDP43 M337V and Q331K disease variants with the isogenic iCell Motor Neurons derived from an apparently healthy normal identifying key pathways altered by TDP43 mutations. Differentially expressed gene (DEG) analysis identified 1810 genes that were altered by the M337V mutation and 1533 genes altered by the Q331K mutation in iPSC-derived human motor neurons in which 1253 DEGs were common between the two mutation as shown in the Venn diagram.

Pathways Altered in iCell Motor Neurons TDP43 M3337V

Pathway analysis identified both up and down-regulated pathways (activated and suppressed, respectively) in which common pathways are shared by each mutation that can serve as druggable targets.

Figure 3A: Pathways Altered in iCell Motor Neurons TDP43 M3337V

Figure 3B: Pathways Altered in iCell Motor Neurons TDP43 Q331K

Pathways Altered in iCell Motor Neurons TDP43 Q331K

Pathway analysis identified both up and down-regulated pathways (activated and suppressed, respectively) in which common pathways are shared by each mutation that can serve as druggable targets.

iCell Motor Neurons ALS TDP43 Disease Models Reveal Altered Connectivity Compared to the Isogenic iCell Motor Neurons

Using MEA, iCell Motor Neurons ALS TDP43 mutations were shown to affect functional connectivity and alter mean firing rate and network burst frequency.

Figure 4: iCell Motor Neurons ALS TDP43 Disease Models Reveal Altered Connectivity Compared to the Isogenic iCell Motor Neurons

Product Highlights

Highly pure

iCell Motor Neurons ALS TDP43 are highly pure cholinergic human motor neurons that are ≥90% β-III tubulin+/Nestin- and ≥70% Isl1/2 at 14 days in vitro. These proteins also express characteristic markers of motor neurons including Isl1, AchR, C9or72, VAChT, and FoxP1.

Homogenous and reproducible

iCell Motor Neurons ALS TDP43 undergo rigorous quality control testing ensure the same performance with every batch of cells.

Rapid results

iCell Motor Neurons ALS TDP43 are shipped cryopreserved with optimized media. Simply thaw and use.

Publications