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| Status |
Public on Sep 27, 2023 |
| Title |
A self-renewing biomimetic skeletal muscle construct engineered using induced myogenic progenitor cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Skeletal muscle is a highly organized and regenerative tissue that maintains its homeostasis primarily by activation and differentiation of muscle stem cells. Mimicking an in vitro skeletal muscle differentiation program that contains self-renewing adult muscle stem cells and aligned myotubes has been challenging. Here, we set out to engineer a biomimetic skeletal muscle construct that can self-regenerate and produce aligned myotubes using induced myogenic progenitor cells (iMPCs), a heterogeneous culture consisting of skeletal muscle stem, progenitor and differentiated cells. Utilizing electrospinning, we fabricated polycaprolactone (PCL) substrates that enabled iMPC-differentiation into aligned myotubes by controlling PCL fiber orientation. Newly-conceived constructs contained highly organized multinucleated myotubes in conjunction with self-renewing muscle stem cells, whose differentiation capacity was augmented by Matrigel supplementation. Additionally, we demonstrate using single cell RNA sequencing (scRNA-seq) that iMPC-derived constructs faithfully recapitulate a step-wise myogenic differentiation program. Notably, when the constructs were subjected to a damaging myonecrotic agent, self-renewing muscle stem cells rapidly differentiated into aligned myotubes, akin to skeletal muscle repair in vivo. Taken together, we report on a novel in vitro system that mirrors myogenic regeneration and muscle fiber alignment, and can serve as a platform to study myogenesis, model muscular dystrophies or perform drug screens.
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| Overall design |
Single cell transcriptional analysis of induced myogenic progenitors (iMPCs) grown on electrospun PCL substrates with or without Matrigel
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| Web link |
https://onlinelibrary.wiley.com/doi/full/10.1002/adfm.202300571
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| Contributor(s) |
Kim I, Lee SS, Ghosh A, Bar-Nur O |
| Citation missing |
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| |
| Submission date |
Jan 04, 2023 |
| Last update date |
Apr 08, 2024 |
| Contact name |
Adhideb Ghosh |
| E-mail(s) |
adhideb.ghosh@hest.ethz.ch
|
| Organization name |
ETH Zurich
|
| Department |
Health Sciences and Technology
|
| Lab |
Translational Nutrition Biology
|
| Street address |
Schorenstrasse 16
|
| City |
Schwerzenbach |
| ZIP/Postal code |
8603 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (2) |
| GSM6916804 |
iMPCs grown on aligned PCL electrospun substrate without Matrigel |
| GSM6916805 |
iMPCs grown on aligned PCL electrospun substrate with Matrigel |
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| Relations |
| BioProject |
PRJNA918395 |
