Pattern of Functional TTX-Resistant Sodium Channels Reveals a Developmental Stage of Human iPSC- and ESC-Derived Nociceptors
Human pluripotent stem cells (hPSCs) offer the opportunity to generate neuronal cells, including nociceptors. Using a chemical-based approach, we generated nociceptive sensory neurons from HUES6 embryonic stem cells and retrovirally reprogrammed induced hPSCs derived from fibroblasts. The nociceptiv...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2015-09-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671115002167 |
| _version_ | 1818206217450815488 |
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| author | Esther Eberhardt Steven Havlicek Diana Schmidt Andrea S. Link Cristian Neacsu Zacharias Kohl Martin Hampl Andreas M. Kist Alexandra Klinger Carla Nau Jürgen Schüttler Christian Alzheimer Jürgen Winkler Barbara Namer Beate Winner Angelika Lampert |
| author_facet | Esther Eberhardt Steven Havlicek Diana Schmidt Andrea S. Link Cristian Neacsu Zacharias Kohl Martin Hampl Andreas M. Kist Alexandra Klinger Carla Nau Jürgen Schüttler Christian Alzheimer Jürgen Winkler Barbara Namer Beate Winner Angelika Lampert |
| author_sort | Esther Eberhardt |
| collection | DOAJ |
| description | Human pluripotent stem cells (hPSCs) offer the opportunity to generate neuronal cells, including nociceptors. Using a chemical-based approach, we generated nociceptive sensory neurons from HUES6 embryonic stem cells and retrovirally reprogrammed induced hPSCs derived from fibroblasts. The nociceptive neurons expressed respective markers and showed tetrodotoxin-sensitive (TTXs) and -resistant (TTXr) voltage-gated sodium currents in patch-clamp experiments. In contrast to their counterparts from rodent dorsal root ganglia, TTXr currents of hPSC-derived nociceptors unexpectedly displayed a significantly more hyperpolarized voltage dependence of activation and fast inactivation. This apparent discrepancy is most likely due to a substantial expression of the developmentally important sodium channel NAV1.5. In view of the obstacles to recapitulate neuropathic pain in animal models, our data advance hPSC-derived nociceptors as a better model to study developmental and pathogenetic processes in human nociceptive neurons and to develop more specific small molecules to attenuate pain. |
| first_indexed | 2024-12-12T04:09:31Z |
| format | Article |
| id | doaj.art-7b938d91ddc44b31834122252d74feb0 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-12T04:09:31Z |
| publishDate | 2015-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-7b938d91ddc44b31834122252d74feb02022-12-22T00:38:41ZengElsevierStem Cell Reports2213-67112015-09-015330531310.1016/j.stemcr.2015.07.010Pattern of Functional TTX-Resistant Sodium Channels Reveals a Developmental Stage of Human iPSC- and ESC-Derived NociceptorsEsther Eberhardt0Steven Havlicek1Diana Schmidt2Andrea S. Link3Cristian Neacsu4Zacharias Kohl5Martin Hampl6Andreas M. Kist7Alexandra Klinger8Carla Nau9Jürgen Schüttler10Christian Alzheimer11Jürgen Winkler12Barbara Namer13Beate Winner14Angelika Lampert15Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, 91054 Erlangen, GermanyIZKF Junior Research Group and BMBF Research Group Neuroscience, IZKF, Friedrich-Alexander-Universität Erlangen-Nürnberg, Glückstrasse 6, 91054 Erlangen, GermanyInstitute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, 91054 Erlangen, GermanyInstitute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, 91054 Erlangen, GermanyInstitute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, 91054 Erlangen, GermanyDepartment of Molecular Neurology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, GermanyInstitute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, 91054 Erlangen, GermanyInstitute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, 91054 Erlangen, GermanyInstitute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, 91054 Erlangen, GermanyDepartment of Anesthesiology and Intensive Care, University Medical Center Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23538 Lübeck, GermanyDepartment of Anesthesiology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstrasse 12, 91054 Erlangen, GermanyInstitute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, 91054 Erlangen, GermanyDepartment of Molecular Neurology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, GermanyInstitute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, 91054 Erlangen, GermanyIZKF Junior Research Group and BMBF Research Group Neuroscience, IZKF, Friedrich-Alexander-Universität Erlangen-Nürnberg, Glückstrasse 6, 91054 Erlangen, GermanyInstitute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, 91054 Erlangen, GermanyHuman pluripotent stem cells (hPSCs) offer the opportunity to generate neuronal cells, including nociceptors. Using a chemical-based approach, we generated nociceptive sensory neurons from HUES6 embryonic stem cells and retrovirally reprogrammed induced hPSCs derived from fibroblasts. The nociceptive neurons expressed respective markers and showed tetrodotoxin-sensitive (TTXs) and -resistant (TTXr) voltage-gated sodium currents in patch-clamp experiments. In contrast to their counterparts from rodent dorsal root ganglia, TTXr currents of hPSC-derived nociceptors unexpectedly displayed a significantly more hyperpolarized voltage dependence of activation and fast inactivation. This apparent discrepancy is most likely due to a substantial expression of the developmentally important sodium channel NAV1.5. In view of the obstacles to recapitulate neuropathic pain in animal models, our data advance hPSC-derived nociceptors as a better model to study developmental and pathogenetic processes in human nociceptive neurons and to develop more specific small molecules to attenuate pain.http://www.sciencedirect.com/science/article/pii/S2213671115002167 |
| spellingShingle | Esther Eberhardt Steven Havlicek Diana Schmidt Andrea S. Link Cristian Neacsu Zacharias Kohl Martin Hampl Andreas M. Kist Alexandra Klinger Carla Nau Jürgen Schüttler Christian Alzheimer Jürgen Winkler Barbara Namer Beate Winner Angelika Lampert Pattern of Functional TTX-Resistant Sodium Channels Reveals a Developmental Stage of Human iPSC- and ESC-Derived Nociceptors Stem Cell Reports |
| title | Pattern of Functional TTX-Resistant Sodium Channels Reveals a Developmental Stage of Human iPSC- and ESC-Derived Nociceptors |
| title_full | Pattern of Functional TTX-Resistant Sodium Channels Reveals a Developmental Stage of Human iPSC- and ESC-Derived Nociceptors |
| title_fullStr | Pattern of Functional TTX-Resistant Sodium Channels Reveals a Developmental Stage of Human iPSC- and ESC-Derived Nociceptors |
| title_full_unstemmed | Pattern of Functional TTX-Resistant Sodium Channels Reveals a Developmental Stage of Human iPSC- and ESC-Derived Nociceptors |
| title_short | Pattern of Functional TTX-Resistant Sodium Channels Reveals a Developmental Stage of Human iPSC- and ESC-Derived Nociceptors |
| title_sort | pattern of functional ttx resistant sodium channels reveals a developmental stage of human ipsc and esc derived nociceptors |
| url | http://www.sciencedirect.com/science/article/pii/S2213671115002167 |
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