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Developmental and functional nature of human iPSC derived motoneurons

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vts_8924_13376.pdf (6.746Mb)
145 S.
Veröffentlichung
2014-04-24
Authors
Stockmann, Marianne
Dissertation


Faculties
Medizinische Fakultät
Abstract
Human induced pluripotent stem cell (hiPSC) derived motoneurons represent a crucial cellular tool to investigate developmental as well as neuropathological mechanisms. Moreover, they can serve as a new platform for drug-screening and -development. We established an effective protocol to generate motoneurons from hiPS cells obtained from hair keratinocytes. Human motoneurons differentiate about 10 times slower compared to rodent motoneurons, the sequential steps of maturation are, however, essentially identical. The polar differentiation of neurites into dendrites and axons occurred after 2 weeks, electrophysiological properties of motoneurons including spontaneous action potentials were detectable 3 weeks later. Synaptic contacts characterized by pre- and postsynaptic marker proteins were observed after 6-7 weeks in culture. Co-culturing of human motoneurons with myotubes for three weeks induced synchronized contractions of differentiated striated muscle cells and the establishment of functional neuromuscular junctions. Our study introduces a model system to study the neuromuscular interplay in vitro and provides the basis to study the physiology and pathophysiology of the human motor system particularly with respect to motoneuron diseases.
Date created
2012
Subject headings
[GND]: Motoneuron
[MeSH]: Induced pluripotent stem cells | Synapses
[Free subject headings]: hiPSCs
[DDC subject group]: DDC 610 / Medicine & health
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https://oparu.uni-ulm.de/xmlui/license_v3

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DOI & citation

Please use this identifier to cite or link to this item: http://dx.doi.org/10.18725/OPARU-3082

Stockmann, Marianne (2014): Developmental and functional nature of human iPSC derived motoneurons. Open Access Repositorium der Universität Ulm und Technischen Hochschule Ulm. Dissertation. http://dx.doi.org/10.18725/OPARU-3082
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