hiPSC-Derived Schwann Cells Influence Myogenic Differentiation in Neuromuscular Cocultures
Motoneurons, skeletal muscle fibers, and Schwann cells form synapses, termed neuromuscular junctions (NMJs). These control voluntary body movement and are affected in numerous neuromuscular diseases. Therefore, a variety of NMJ in vitro models have been explored to enable mechanistic and pharmacolog...
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MDPI AG
2021-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/12/3292 |
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| author | Sarah Janice Hörner Nathalie Couturier Roman Bruch Philipp Koch Mathias Hafner Rüdiger Rudolf |
| author_facet | Sarah Janice Hörner Nathalie Couturier Roman Bruch Philipp Koch Mathias Hafner Rüdiger Rudolf |
| author_sort | Sarah Janice Hörner |
| collection | DOAJ |
| description | Motoneurons, skeletal muscle fibers, and Schwann cells form synapses, termed neuromuscular junctions (NMJs). These control voluntary body movement and are affected in numerous neuromuscular diseases. Therefore, a variety of NMJ in vitro models have been explored to enable mechanistic and pharmacological studies. So far, selective integration of Schwann cells in these models has been hampered, due to technical limitations. Here we present robust protocols for derivation of Schwann cells from human induced pluripotent stem cells (hiPSC) and their coculture with hiPSC-derived motoneurons and C2C12 muscle cells. Upon differentiation with tuned BMP signaling, Schwann cells expressed marker proteins, S100b, Gap43, vimentin, and myelin protein zero. Furthermore, they displayed typical spindle-shaped morphologies with long processes, which often aligned with motoneuron axons. Inclusion of Schwann cells in coculture experiments with hiPSC-derived motoneurons and C2C12 myoblasts enhanced myotube growth and affected size and number of acetylcholine receptor plaques on myotubes. Altogether, these data argue for the availability of a consistent differentiation protocol for Schwann cells and their amenability for functional integration into neuromuscular in vitro models, fostering future studies of neuromuscular mechanisms and disease. |
| first_indexed | 2024-03-10T04:26:07Z |
| format | Article |
| id | doaj.art-ba99645122cc4ddb88da6cc50801a284 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T04:26:07Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-ba99645122cc4ddb88da6cc50801a2842023-11-23T07:35:47ZengMDPI AGCells2073-44092021-11-011012329210.3390/cells10123292hiPSC-Derived Schwann Cells Influence Myogenic Differentiation in Neuromuscular CoculturesSarah Janice Hörner0Nathalie Couturier1Roman Bruch2Philipp Koch3Mathias Hafner4Rüdiger Rudolf5Institute of Molecular and Cell Biology, Mannheim University of Applied Sciences, 68163 Mannheim, GermanyInstitute of Molecular and Cell Biology, Mannheim University of Applied Sciences, 68163 Mannheim, GermanyInstitute of Molecular and Cell Biology, Mannheim University of Applied Sciences, 68163 Mannheim, GermanyCentral Institute of Mental Health, Medical Faculty Mannheim of Heidelberg University, 68159 Mannheim, GermanyInstitute of Molecular and Cell Biology, Mannheim University of Applied Sciences, 68163 Mannheim, GermanyInstitute of Molecular and Cell Biology, Mannheim University of Applied Sciences, 68163 Mannheim, GermanyMotoneurons, skeletal muscle fibers, and Schwann cells form synapses, termed neuromuscular junctions (NMJs). These control voluntary body movement and are affected in numerous neuromuscular diseases. Therefore, a variety of NMJ in vitro models have been explored to enable mechanistic and pharmacological studies. So far, selective integration of Schwann cells in these models has been hampered, due to technical limitations. Here we present robust protocols for derivation of Schwann cells from human induced pluripotent stem cells (hiPSC) and their coculture with hiPSC-derived motoneurons and C2C12 muscle cells. Upon differentiation with tuned BMP signaling, Schwann cells expressed marker proteins, S100b, Gap43, vimentin, and myelin protein zero. Furthermore, they displayed typical spindle-shaped morphologies with long processes, which often aligned with motoneuron axons. Inclusion of Schwann cells in coculture experiments with hiPSC-derived motoneurons and C2C12 myoblasts enhanced myotube growth and affected size and number of acetylcholine receptor plaques on myotubes. Altogether, these data argue for the availability of a consistent differentiation protocol for Schwann cells and their amenability for functional integration into neuromuscular in vitro models, fostering future studies of neuromuscular mechanisms and disease.https://www.mdpi.com/2073-4409/10/12/3292AChRacetylcholine receptorshiPSCin vitroneural crestneuromuscular junction |
| spellingShingle | Sarah Janice Hörner Nathalie Couturier Roman Bruch Philipp Koch Mathias Hafner Rüdiger Rudolf hiPSC-Derived Schwann Cells Influence Myogenic Differentiation in Neuromuscular Cocultures Cells AChR acetylcholine receptors hiPSC in vitro neural crest neuromuscular junction |
| title | hiPSC-Derived Schwann Cells Influence Myogenic Differentiation in Neuromuscular Cocultures |
| title_full | hiPSC-Derived Schwann Cells Influence Myogenic Differentiation in Neuromuscular Cocultures |
| title_fullStr | hiPSC-Derived Schwann Cells Influence Myogenic Differentiation in Neuromuscular Cocultures |
| title_full_unstemmed | hiPSC-Derived Schwann Cells Influence Myogenic Differentiation in Neuromuscular Cocultures |
| title_short | hiPSC-Derived Schwann Cells Influence Myogenic Differentiation in Neuromuscular Cocultures |
| title_sort | hipsc derived schwann cells influence myogenic differentiation in neuromuscular cocultures |
| topic | AChR acetylcholine receptors hiPSC in vitro neural crest neuromuscular junction |
| url | https://www.mdpi.com/2073-4409/10/12/3292 |
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