ArticlePloS one2014
Neurotrophic requirements of human motor neurons defined using amplified and purified stem cell-derived cultures.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
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- Neurotrophic factors in the physiology of motor neurons and their role in the pathobiology and therapeutic approach to amyotrophic lateral sclerosis.Frontiers in molecular neuroscience · 2023Review
- Efficacy of clinical-grade human placental mesenchymal stromal cells in fetal ovine myelomeningocele repair.Journal of pediatric surgery · 2022Article
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- Advancing precision medicines for ocular disorders: Diagnostic genomics to tailored therapies.Frontiers in medicine · 2022Review
- Using 2D and 3D pluripotent stem cell models to study neurotropic viruses.Frontiers in virology (Lausanne, Switzerland) · 2022Article
- Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances and Future Directions.Cancers · 2021Review
- Engineering skeletal muscle tissues with advanced maturity improves synapse formation with human induced pluripotent stem cell-derived motor neurons.APL bioengineering · 2021Article
- Mouse Embryonic Stem Cells Expressing GDNF Show Enhanced Dopaminergic Differentiation and Promote Behavioral Recovery After Grafting in Parkinsonian Rats.Frontiers in cell and developmental biology · 2021Article
- Full small molecule conversion of human fibroblasts to neuroectodermal cells via a cocktail of Dorsomorphin and Trichostatin A.Regenerative therapy · 2020Article
- Small molecular compounds efficiently convert human fibroblasts directly into neurons.Molecular medicine reports · 2020Article
- In utero treatment of myelomeningocele with placental mesenchymal stromal cells - Selection of an optimal cell line in preparation for clinical trials.Journal of pediatric surgery · 2020Article
- LCM-seq reveals unique transcriptional adaptation mechanisms of resistant neurons and identifies protective pathways in spinal muscular atrophy.Genome research · 2020Article
- Direct Conversion of Human Urine Cells to Neurons by Small Molecules.Scientific reports · 2019Article
- Isolation and Culture of Oculomotor, Trochlear, and Spinal Motor Neurons from Prenatal Islmn:GFP Transgenic Mice.Journal of visualized experiments : JoVE · 2019Article
- FGF family members differentially regulate maturation and proliferation of stem cell-derived astrocytes.Scientific reports · 2019Article
- Systematic Comparison of Retinal Organoid Differentiation from Human Pluripotent Stem Cells Reveals Stage Specific, Cell Line, and Methodological Differences.Stem cells translational medicine · 2019Article
- The molecular pathogenesis of superoxide dismutase 1-linked ALS is promoted by low oxygen tension.Acta neuropathologica · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human motor neurons derived from embryonic and induced pluripotent stem cells (hESCs and hiPSCs) are a potentially important tool for studying motor neuron survival and pathological cell death. However, their basic survival requirements remain poorly characterized. Here, we sought to optimize a robust survival assay and characterize their response to different neurotrophic factors. First, to increase motor neuron yield, we screened a small-molecule collection and found that the Rho-associated kinase (ROCK) inhibitor Y-27632 enhances motor neuron progenitor proliferation up to 4-fold in hESC and hiPSC cultures. Next, we FACS-purified motor neurons expressing the Hb9::GFP reporter from Y-27632-amplified embryoid bodies and cultured them in the presence of mitotic inhibitors to eliminate dividing progenitors. Survival of these purified motor neurons in the absence of any other cell type was strongly dependent on neurotrophic support. GDNF, BDNF and CNTF all showed potent survival effects (EC(50) 1-2 pM). The number of surviving motor neurons was further enhanced in the presence of forskolin and IBMX, agents that increase endogenous cAMP levels. As a demonstration of the ability of the assay to detect novel neurotrophic agents, Y-27632 itself was found to support human motor neuron survival. Thus, purified human stem cell-derived motor neurons show survival requirements similar to those of primary rodent motor neurons and can be used for rigorous cell-based screening.
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