Modeling ALS and FTD with iPSC-derived neurons

Lee, Sebum; Huang, Eric J.

doi:10.1016/j.brainres.2015.10.003

Cited by 60 publications

(57 citation statements)

References 72 publications

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“…Advances in motor neuron differentiation have been extensively reviewed, including recently [15]. We address the variation in protocol efficiencies by providing a checklist that can be used to evaluate the quality and reproducibility of in vitro differentiation.…”

Section: Introductionmentioning

confidence: 99%

Common pitfalls of stem cell differentiation: a guide to improving protocols for neurodegenerative disease models and research

Engel

Do-Ha

Muñoz

et al. 2016

Cell. Mol. Life Sci.

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Induced pluripotent stem cells and embryonic stem cells have revolutionized cellular neuroscience, providing the opportunity to model neurological diseases and test potential therapeutics in a pre-clinical setting. The power of these models has been widely discussed, but the potential pitfalls of stem cell differentiation in this research are less well described. We have analyzed the literature that describes differentiation of human pluripotent stem cells into three neural cell types that are commonly used to study diseases, including forebrain cholinergic neurons for Alzheimer’s disease, midbrain dopaminergic neurons for Parkinson’s disease and cortical astrocytes for neurodegenerative and psychiatric disorders. Published protocols for differentiation vary widely in the reported efficiency of target cell generation. Additionally, characterization of the cells by expression profile and functionality differs between studies and is often insufficient, leading to highly variable protocol outcomes. We have synthesized this information into a simple methodology that can be followed when performing or assessing differentiation techniques. Finally we propose three considerations for future research, including the use of physiological O2 conditions, three-dimensional co-culture systems and microfluidics to control feeding cycles and growth factor gradients. Following these guidelines will help researchers to ensure that robust and meaningful data is generated, enabling the full potential of stem cell differentiation for disease modeling and regenerative medicine.

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Section: Introductionmentioning

confidence: 99%

Common pitfalls of stem cell differentiation: a guide to improving protocols for neurodegenerative disease models and research

Engel

Do-Ha

Muñoz

et al. 2016

Cell. Mol. Life Sci.

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“…To address examining gene expression in neural tissue, motor neurons derived from patient‐induced pluripotent stem cells (iPSCs) are now being used. Several studies have used iPSC‐derived motor neurons (iPSC‐MNs) to model neuromuscular diseases including ALS (Chen et al., ; Ichiyanagi et al., ; S. Lee & Huang, ), SMA (Fuller et al., ; Nizzardo et al., ) and various IPNs (G. Lee et al., ; Saporta et al., ). iPSCs‐MNs have the potential to model neural specific phenotypic changes, gene expression, and chromatin interactions in disease relevant tissue.…”

Section: Challenges and Future Strategies To Study Sv Causing Ipnsmentioning

confidence: 99%

Structural variations causing inherited peripheral neuropathies: A paradigm for understanding genomic organization, chromatin interactions, and gene dysregulation

Cutrupi

Brewer

Nicholson

et al. 2018

Molec Gen & Gen Med

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Inherited peripheral neuropathies (IPNs) are a clinically and genetically heterogeneous group of diseases affecting the motor and sensory peripheral nerves. IPNs have benefited from gene discovery and genetic diagnosis using next‐generation sequencing with over 80 causative genes available for testing. Despite this success, up to 50% of cases remain genetically unsolved. In the absence of protein coding mutations, noncoding DNA or structural variation (SV) mutations are a possible explanation. The most common IPN, Charcot‐Marie‐Tooth neuropathy type 1A (CMT1A), is caused by a 1.5 Mb duplication causing trisomy of the dosage sensitive gene PMP22. Using genome sequencing, we recently identified two large genomic rearrangements causing IPN subtypes X‐linked CMT (CMTX3) and distal hereditary motor neuropathy (DHMN1), thereby expanding the spectrum of SV mutations causing IPN. Understanding how newly discovered SVs can cause IPN may serve as a useful paradigm to examine the role of topologically associated domains (TADs), chromatin interactions, and gene dysregulation in disease. This review will describe the growing role of SV in the pathogenesis of IPN and the importance of considering this type of mutation in Mendelian diseases where protein coding mutations cannot be identified.

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“…1 Neuromuscular disorders can be segregated into motor-neuron diseases like amyotrophic lateral sclerosis (ALS), 2 spinal muscular atrophy (SMA); 3 muscular ailments…”

Section: Editorialmentioning

confidence: 99%