Electrical maturation of neurons derived from human embryonic stem cells [v2; ref status: indexed, http://f1000r.es/4gy]
In-vitro neuronal differentiation of human pluripotent stem cells has become a widely used tool in disease modeling and prospective regenerative medicine. Most studies evaluate neurons molecularly and only a handful of them use electrophysiological tools to directly indicate that these are genuine n...
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2014-10-01
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| Series: | F1000Research |
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| Online Access: | http://f1000research.com/articles/3-196/v2 |
| _version_ | 1828889316113252352 |
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| author | Michael Telias Menahem Segal Dalit Ben-Yosef |
| author_facet | Michael Telias Menahem Segal Dalit Ben-Yosef |
| author_sort | Michael Telias |
| collection | DOAJ |
| description | In-vitro neuronal differentiation of human pluripotent stem cells has become a widely used tool in disease modeling and prospective regenerative medicine. Most studies evaluate neurons molecularly and only a handful of them use electrophysiological tools to directly indicate that these are genuine neurons. Therefore, the specific timing of development of intrinsic electrophysiological properties and synaptic capabilities remains poorly understood. Here we describe a systematic analysis of developing neurons derived in-vitro from human embryonic stem cells (hESCs). We show that hESCs differentiated in-vitro into early embryonic neurons, displaying basically mature morphological and electrical features as early as day 37. This early onset of action potential discharges suggests that first stages of neurogenesis in humans are already associated with electrical maturation. Spike frequency, amplitude, duration, threshold and after hyperpolarization were found to be the most predictive parameters for electrical maturity. Furthermore, we were able to detect spontaneous synaptic activity already at these early time-points, demonstrating that neuronal connectivity can develop concomitantly with the gradual process of electrical maturation. These results highlight the functional properties of hESCs in the process of their development into neurons. Moreover, our results provide practical tools for the direct measurement of functional maturity, which can be reproduced and implemented for stem cell research of neurogenesis in general, and neurodevelopmental disorders in particular. |
| first_indexed | 2024-12-13T12:39:11Z |
| format | Article |
| id | doaj.art-c625102fe6434a079da6df3aa2deef4d |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-12-13T12:39:11Z |
| publishDate | 2014-10-01 |
| publisher | F1000 Research Ltd |
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| spelling | doaj.art-c625102fe6434a079da6df3aa2deef4d2022-12-21T23:45:42ZengF1000 Research LtdF1000Research2046-14022014-10-01310.12688/f1000research.4943.25794Electrical maturation of neurons derived from human embryonic stem cells [v2; ref status: indexed, http://f1000r.es/4gy]Michael Telias0Menahem Segal1Dalit Ben-Yosef2Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, 64239, IsraelDepartment of Neurobiology, Weizmann Institute of Science, Rehovot, 76100, IsraelDepartment of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, 64239, IsraelIn-vitro neuronal differentiation of human pluripotent stem cells has become a widely used tool in disease modeling and prospective regenerative medicine. Most studies evaluate neurons molecularly and only a handful of them use electrophysiological tools to directly indicate that these are genuine neurons. Therefore, the specific timing of development of intrinsic electrophysiological properties and synaptic capabilities remains poorly understood. Here we describe a systematic analysis of developing neurons derived in-vitro from human embryonic stem cells (hESCs). We show that hESCs differentiated in-vitro into early embryonic neurons, displaying basically mature morphological and electrical features as early as day 37. This early onset of action potential discharges suggests that first stages of neurogenesis in humans are already associated with electrical maturation. Spike frequency, amplitude, duration, threshold and after hyperpolarization were found to be the most predictive parameters for electrical maturity. Furthermore, we were able to detect spontaneous synaptic activity already at these early time-points, demonstrating that neuronal connectivity can develop concomitantly with the gradual process of electrical maturation. These results highlight the functional properties of hESCs in the process of their development into neurons. Moreover, our results provide practical tools for the direct measurement of functional maturity, which can be reproduced and implemented for stem cell research of neurogenesis in general, and neurodevelopmental disorders in particular.http://f1000research.com/articles/3-196/v2Morphogenesis & Cell BiologyNeurodevelopmentNeuronal & Glial Cell BiologyStem Cells & Regeneration |
| spellingShingle | Michael Telias Menahem Segal Dalit Ben-Yosef Electrical maturation of neurons derived from human embryonic stem cells [v2; ref status: indexed, http://f1000r.es/4gy] F1000Research Morphogenesis & Cell Biology Neurodevelopment Neuronal & Glial Cell Biology Stem Cells & Regeneration |
| title | Electrical maturation of neurons derived from human embryonic stem cells [v2; ref status: indexed, http://f1000r.es/4gy] |
| title_full | Electrical maturation of neurons derived from human embryonic stem cells [v2; ref status: indexed, http://f1000r.es/4gy] |
| title_fullStr | Electrical maturation of neurons derived from human embryonic stem cells [v2; ref status: indexed, http://f1000r.es/4gy] |
| title_full_unstemmed | Electrical maturation of neurons derived from human embryonic stem cells [v2; ref status: indexed, http://f1000r.es/4gy] |
| title_short | Electrical maturation of neurons derived from human embryonic stem cells [v2; ref status: indexed, http://f1000r.es/4gy] |
| title_sort | electrical maturation of neurons derived from human embryonic stem cells v2 ref status indexed http f1000r es 4gy |
| topic | Morphogenesis & Cell Biology Neurodevelopment Neuronal & Glial Cell Biology Stem Cells & Regeneration |
| url | http://f1000research.com/articles/3-196/v2 |
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