title: Modeling Axonal Phenotypes with Human Pluripotent Stem Cells.
abstract: Impaired axonal development and degeneration are implicated in many debilitating disorders, such as hereditary spastic paraplegia (HSP), amyotrophic lateral sclerosis (ALS), and periphery neuropathy. Human pluripotent stem cells (hPSCs) have provided researchers with an excellent resource for modeling human neuropathologic processes including axonal defects in vitro. There are a number of steps that are crucial when developing an hPSC-based model of a human disease, including generating induced pluripotent stem cells (iPSCs), differentiating those cells to affected cell types, and identifying disease-relevant phenotypes. Here, we describe these steps in detail, focusing on the neurodegenerative disorder HSP.
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT, 06030, USA.
authors.forename: Kyle R
authors.initials: KR
authors.lastname: Denton
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT, 06030, USA.
authors.forename: Chong-Chong
authors.initials: CC
authors.lastname: Xu
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT, 06030, USA. xjli@uchc.edu.|The Stem Cell Institute, University of Connecticut Health Center, Farmington, CT, 06032, USA. xjli@uchc.edu.
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Li
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure*; D015415:Biomarkers / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D065150:Cellular Reprogramming / Q000187:drug effects; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D061252:Feeder Cells / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007797:Laminin / Q000737:chemistry; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure*; D008954:Models, Biological; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D061251:Primary Cell Culture; D011509:Proteoglycans / Q000737:chemistry; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D004338:Drug Combinations; D005136:Eye Proteins; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018398:Homeodomain Proteins; C583557:IGF1 protein, human; D007797:Laminin; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D011509:Proteoglycans; D012097:Repressor Proteins; C059485:matrigel; D007334:Insulin-Like Growth Factor I; C579455:BDNF protein, human; D003094:Collagen
keywords: Axon; Degeneration; Mitochondria; hESCs; iPSCs