title: Accelerated neuronal differentiation toward motor neuron lineage from human embryonic stem cell line (H9).
abstract: Motor neurons loss plays a pivotal role in the pathoetiology of various debilitating diseases such as, but not limited to, amyotrophic lateral sclerosis, primary lateral sclerosis, progressive muscular atrophy, progressive bulbar palsy, pseudobulbar palsy, and spinal muscular atrophy. However, advancement in motor neuron replacement therapy has been significantly constrained by the difficulties in large-scale production at a cost-effective manner. Current methods to derive motor neuron heavily rely on biochemical stimulation, chemical biological screening, and complex physical cues. These existing methods are seriously challenged by extensive time requirements and poor yields. An innovative approach that overcomes prior hurdles and enhances the rate of successful motor neuron transplantation in patients is of critical demand. Iron, a trace element, is indispensable for the normal development and function of the central nervous system. Whether ferric ions promote neuronal differentiation and subsequently promote motor neuron lineage has never been considered. Here, we demonstrate that elevated iron concentration can drastically accelerate the differentiation of human embryonic stem cells (hESCs) toward motor neuron lineage potentially via a transferrin mediated pathway. HB9 expression in 500 nM iron-treated hESCs is approximately twofold higher than the control. Moreover, iron treatment generated more matured and functional motor neuron-like cells that are ∼1.5 times more sensitive to depolarization when compared to the control. Our methodology renders an expedited approach to harvest motor neuron-like cells for disease, traumatic injury regeneration, and drug screening.
authors.affiliation: 1 Bioengineering Program, School of Engineering, University of California , Merced, California.
authors.forename: David
authors.initials: D
authors.lastname: Lu
authors.forename: Eric Y T
authors.initials: EY
authors.lastname: Chen
authors.forename: Philip
authors.initials: P
authors.lastname: Lee
authors.forename: Yung-Chen
authors.initials: YC
authors.lastname: Wang
authors.forename: Wendy
authors.initials: W
authors.lastname: Ching
authors.forename: Christopher
authors.initials: C
authors.lastname: Markey
authors.forename: Chase
authors.initials: C
authors.lastname: Gulstrom
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Chen
authors.forename: Thien
authors.initials: T
authors.lastname: Nguyen
authors.forename: Wei-Chun
authors.initials: WC
authors.lastname: Chin
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D019070:Cell Lineage / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007501:Iron / Q000494:pharmacology; D051379:Mice; D009046:Motor Neurons / Q000166:cytology* / Q000187:drug effects; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014168:Transferrin / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D014168:Transferrin; D007501:Iron