Immobilized NRG1 Accelerates Neural Crest like Cell Differentiation Toward Functional Schwann Cells Through Sustained Erk1/2 Activation and YAP/TAZ Nuclear Translocation
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Wiley
2024
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| author | Georgios Tseropoulos Pihu Mehrotra Ashis Kumer Podder Emma Wilson Yali Zhang Jianmin Wang Alison Koontz Nan Papili Gao Rudiyanto Gunawan Song Liu Laura M. Feltri Marianne E. Bronner Stelios T. Andreadis |
| author_facet | Georgios Tseropoulos Pihu Mehrotra Ashis Kumer Podder Emma Wilson Yali Zhang Jianmin Wang Alison Koontz Nan Papili Gao Rudiyanto Gunawan Song Liu Laura M. Feltri Marianne E. Bronner Stelios T. Andreadis Georgios Tseropoulos Pihu Mehrotra Ashis Kumer Podder Emma Wilson Yali Zhang Jianmin Wang Alison Koontz Nan Papili Gao Rudiyanto Gunawan Song Liu Laura M. Feltri Marianne E. Bronner Stelios T. Andreadis |
| collection | Wiley Open Access |
| contents | Immobilized NRG1 Accelerates Neural Crest like Cell Differentiation Toward Functional Schwann Cells Through Sustained Erk1/2 Activation and YAP/TAZ Nuclear Translocation Georgios Tseropoulos Pihu Mehrotra Ashis Kumer Podder Emma Wilson Yali Zhang Jianmin Wang Alison Koontz Nan Papili Gao Rudiyanto Gunawan Song Liu Laura M. Feltri Marianne E. Bronner Stelios T. Andreadis Advanced Science AbstractNeural Crest cells (NC) are a multipotent cell population that give rise to a multitude of cell types including Schwann cells (SC) in the peripheral nervous system (PNS). Immature SC interact with neuronal axons via the neuregulin 1 (NRG1) ligand present on the neuronal surface and ultimately form the myelin sheath. Multiple attempts to derive functional SC from pluripotent stem cells have met challenges with respect to expression of mature markers and axonal sorting. Here, they hypothesized that sustained signaling from immobilized NRG1 (iNRG1) might enhance the differentiation of NC derived from glabrous neonatal epidermis towards a SC phenotype. Using this strategy, NC derived SC expressed mature markers to similar levels as compared to explanted rat sciatic SC. Signaling studies revealed that sustained NRG1 signaling led to yes‐associated protein 1 (YAP) activation and nuclear translocation. Furthermore, NC derived SC on iNRG1 exhibited mature SC function as they aligned with rat dorsal root ganglia (DRG) neurons in an in vitro coculture model; and most notably, aligned on neuronal axons upon implantation in a chick embryo model in vivo. Taken together their work demonstrated the importance of signaling dynamics in SC differentiation, aiming towards development of drug testing platforms for de‐myelinating disorders. 10.1002/advs.202402607 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1002/advs.202402607 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_advs_202402607 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Immobilized NRG1 Accelerates Neural Crest like Cell Differentiation Toward Functional Schwann Cells Through Sustained Erk1/2 Activation and YAP/TAZ Nuclear Translocation Georgios Tseropoulos Pihu Mehrotra Ashis Kumer Podder Emma Wilson Yali Zhang Jianmin Wang Alison Koontz Nan Papili Gao Rudiyanto Gunawan Song Liu Laura M. Feltri Marianne E. Bronner Stelios T. Andreadis Advanced Science Immobilized NRG1 Accelerates Neural Crest like Cell Differentiation Toward Functional Schwann Cells Through Sustained Erk1/2 Activation and YAP/TAZ Nuclear Translocation Georgios Tseropoulos Pihu Mehrotra Ashis Kumer Podder Emma Wilson Yali Zhang Jianmin Wang Alison Koontz Nan Papili Gao Rudiyanto Gunawan Song Liu Laura M. Feltri Marianne E. Bronner Stelios T. Andreadis Advanced Science AbstractNeural Crest cells (NC) are a multipotent cell population that give rise to a multitude of cell types including Schwann cells (SC) in the peripheral nervous system (PNS). Immature SC interact with neuronal axons via the neuregulin 1 (NRG1) ligand present on the neuronal surface and ultimately form the myelin sheath. Multiple attempts to derive functional SC from pluripotent stem cells have met challenges with respect to expression of mature markers and axonal sorting. Here, they hypothesized that sustained signaling from immobilized NRG1 (iNRG1) might enhance the differentiation of NC derived from glabrous neonatal epidermis towards a SC phenotype. Using this strategy, NC derived SC expressed mature markers to similar levels as compared to explanted rat sciatic SC. Signaling studies revealed that sustained NRG1 signaling led to yes‐associated protein 1 (YAP) activation and nuclear translocation. Furthermore, NC derived SC on iNRG1 exhibited mature SC function as they aligned with rat dorsal root ganglia (DRG) neurons in an in vitro coculture model; and most notably, aligned on neuronal axons upon implantation in a chick embryo model in vivo. Taken together their work demonstrated the importance of signaling dynamics in SC differentiation, aiming towards development of drug testing platforms for de‐myelinating disorders. 10.1002/advs.202402607 http://creativecommons.org/licenses/by/4.0/ |
| title | Immobilized NRG1 Accelerates Neural Crest like Cell Differentiation Toward Functional Schwann Cells Through Sustained Erk1/2 Activation and YAP/TAZ Nuclear Translocation |
| topic | Advanced Science |
| url | https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202402607 |