Maturation of spinal motor neurons derived from human embryonic stem cells Journal Article
| Authors: | Takazawa, T.; Croft, G. F.; Amoroso, M. W.; Studer, L.; Wichterle, H.; MacDermott, A. B. |
| Article Title: | Maturation of spinal motor neurons derived from human embryonic stem cells |
| Abstract: | Our understanding of motor neuron biology in humans is derived mainly from investigation of human postmortem tissue and more indirectly from live animal models such as rodents. Thus generation of motor neurons from human embryonic stem cells and human induced pluripotent stem cells is an important new approach to model motor neuron function. To be useful models of human motor neuron function, cells generated in vitro should develop mature properties that are the hallmarks of motor neurons in vivo such as elaborated neuronal processes and mature electrophysiological characteristics. Here we have investigated changes in morphological and electrophysiological properties associated with maturation of neurons differentiated from human embryonic stem cells expressing GFP driven by a motor neuron specific reporter (Hb9::GFP) in culture. We observed maturation in cellular morphology seen as more complex neurite outgrowth and increased soma area over time. Electrophysiological changes included decreasing input resistance and increasing action potential firing frequency over 13 days in vitro. Furthermore, these human embryonic stem cell derived motor neurons acquired two physiological characteristics that are thought to underpin motor neuron integrated function in motor circuits; spike frequency adaptation and rebound action potential firing. These findings show that human embryonic stem cell derived motor neurons develop functional characteristics typical of spinal motor neurons in vivo and suggest that they are a relevant and useful platform for studying motor neuron development and function and for modeling motor neuron diseases. © 2012 Takazawa et al. |
| Keywords: | protein expression; unclassified drug; human cell; cells, cultured; cell structure; cell maturation; embryo; embryonic stem cell; green fluorescent protein; transcription factor; cell differentiation; in vitro study; animalia; transcription factors; motor neurons; embryonic stem cells; spinal cord motoneuron; rodentia; nerve function; morphometrics; nerve cell differentiation; neurogenesis; nerve potential; action potentials; nerve fiber growth; patch clamp; nerve cell membrane potential; whole cell; cellular parameters; biocytin; transcription factor hb9; action potential firing frequency; cell body area; input resistance; nervous system electrophysiology; number of branches; rebound action potential firing; spike frequency adaptation |
| Journal Title: | PLoS ONE |
| Volume: | 7 |
| Issue: | 7 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2012-01-01 |
| Start Page: | e40154 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0040154 |
| PROVIDER: | scopus |
| PMCID: | PMC3388990 |
| PUBMED: | 22802953 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 August 2012" - "Source: Scopus" |
