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| Status |
Public on May 12, 2022 |
| Title |
An Engineered Multicellular Stem Cell Niche for the 3D Derivation of Human Myogenic Progenitors from iPSCs |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Fate decisions in the embryo are controlled by a plethora of microenvironmental interactions in a three-dimensional niche. To investigate whether aspects of this microenvironmental complexity can be engineered to direct myogenic human induced pluripotent stem cell (hiPSC) differentiation, we screened cell types present in the developmental or adult stem cell niche in heterotypic suspension embryoids. We identified embryonic endothelial cells and fibroblasts as highly permissive for myogenic specification of hiPSCs. After two weeks of sequential Wnt and FGF pathway induction, these three-component embryoids (iTCEs) are enriched in Pax7 positive embryonic-like myogenic progenitors (eMPs) that can be isolated by flow cytometry. Myogenic differentiation of hiPSCs in iTCEs relies on a specialized structural microenvironment and depends on MAPK, PI3K/AKT, and Notch signaling. After transplantation in a mouse model of Duchenne muscular dystrophy, eMPs repopulate the stem cell niche, reactivate after repeated injury and, compared to adult human myoblasts, display enhanced fusion and lead to stronger muscles. Altogether, we provide a two-week protocol for efficient and scalable suspension-based 3D derivation of Pax7 positive myogenic progenitors from hiPSCs.
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| Overall design |
QuantSeq from human induced pluripotent stem cell (hiPSC), three-component embryoids (TCEs) which comprise of murine growth arrested embryonic fibroblasts - GAeFib (Fibro), murine embryonic endothelial cells - eEC (Endo) and hiPSCs in comination and alone.
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| Contributor(s) |
Mashinchian O, De Franceschi F, Nassiri S, Michaud J, Migliavacca E, Aouad P, Metairon S, Pruvost S, Karaz S, Fabre P, Molina T, Stuelsatz P, Hegde N, Le Moal E, Dammone G, Dumont NA, Lutolf MP, Feige JN, Bentzinger CF |
| Citation(s) |
35703167 |
| Submission date |
Apr 25, 2022 |
| Last update date |
Jul 06, 2022 |
| Contact name |
Jerome Feige |
| Organization name |
Nestle Institute Of Health Sciences
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| Department |
Musculo-Skeletal Health
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| Street address |
EPFL Innovation Park, Building H
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| City |
Lausanne |
| ZIP/Postal code |
1015 |
| Country |
Switzerland |
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| Platforms (3) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL22245 |
Illumina HiSeq 2500 (Homo sapiens; Mus musculus) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA831685 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE201424_htseq_summary2667_HsOnly_GEO.csv.gz |
382.6 Kb |
(ftp)(http) |
CSV |
| GSE201424_htseq_summary2668_MmOnly_GEO.csv.gz |
407.5 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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