hiPSC-Derived Schwann Cells Influence Myogenic Differentiation in Neuromuscular Cocultures.
Animals
Biomarkers
/ metabolism
Bone Morphogenetic Proteins
/ metabolism
Cell Differentiation
Cell Line
Cell Shape
Coculture Techniques
Humans
Induced Pluripotent Stem Cells
/ cytology
Mice
Muscle Development
Muscle Fibers, Skeletal
/ metabolism
Neuromuscular Junction
/ cytology
Receptors, Cholinergic
/ metabolism
Schwann Cells
/ cytology
Signal Transduction
AChR
NMJ
Schwann cells
acetylcholine receptors
hiPSC
in vitro
neural crest
neuromuscular junction
stem cells
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
24 11 2021
24 11 2021
Historique:
received:
22
10
2021
revised:
20
11
2021
accepted:
21
11
2021
entrez:
24
12
2021
pubmed:
25
12
2021
medline:
21
1
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34943800
pii: cells10123292
doi: 10.3390/cells10123292
pmc: PMC8699767
pii:
doi:
Substances chimiques
Biomarkers
0
Bone Morphogenetic Proteins
0
Receptors, Cholinergic
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Federal Ministry of Education and Research
ID : 03FH8I02IA
Organisme : Federal Ministry of Education and Research
ID : 13FH8I05IA
Organisme : Albert-und-Anneliese-Konanz Stiftung
ID : Hörner
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