iMyoblasts for ex vivo and in vivo investigations of human myogenesis and disease modeling.
Animals
Cell Differentiation
Cell Line
Cell Lineage
Cells, Cultured
Disease Models, Animal
Homeodomain Proteins
/ metabolism
Humans
Induced Pluripotent Stem Cells
/ cytology
Mice
Muscle Development
Muscular Dystrophy, Facioscapulohumeral
/ pathology
Myoblasts
/ transplantation
PAX3 Transcription Factor
/ metabolism
Recovery of Function
Regeneration
developmental biology
human
human ipsc myogenesis
iMyoblasts
mouse
muscle stem cells
regenerative medicine
stem cells
xenograft
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
25 01 2022
25 01 2022
Historique:
received:
13
05
2021
accepted:
10
12
2021
entrez:
25
1
2022
pubmed:
26
1
2022
medline:
5
3
2022
Statut:
epublish
Résumé
Skeletal muscle myoblasts (iMyoblasts) were generated from human induced pluripotent stem cells (iPSCs) using an efficient and reliable transgene-free induction and stem cell selection protocol. Immunofluorescence, flow cytometry, qPCR, digital RNA expression profiling, and scRNA-Seq studies identify iMyoblasts as a Muscular dystrophies are a group of inherited genetic diseases characterised by progressive muscle weakness. They lead to disability or even death, and no cure exists against these conditions. Advances in genome sequencing have identified many mutations that underly muscular dystrophies, opening the door to new therapies that could repair incorrect genes or rebuild damaged muscles. However, testing these ideas requires better ways to recreate human muscular dystrophy in the laboratory. One strategy for modelling muscular dystrophy involves coaxing skin or other cells from an individual into becoming ‘induced pluripotent stem cells’; these can then mature to form almost any adult cell in the body, including muscles. However, this approach does not usually create myoblasts, the ‘precursor’ cells that specifically mature into muscle during development. This limits investigations into how disease-causing mutations impact muscle formation early on. As a response, Guo et al. developed a two-step protocol of muscle maturation followed by stem cell growth selection to isolate and grow ‘induced myoblasts’ from induced pluripotent stem cells taken from healthy volunteers and muscular dystrophy patients. These induced myoblasts can both make more of themselves and become muscle, allowing Guo et al. to model three different types of muscular dystrophy. These myoblasts also behave as stem cells when grafted inside adult mouse muscles: some formed human muscle tissue while others remained as precursor cells, which could then respond to muscle injury and start repair. The induced myoblasts developed by Guo et al. will enable scientists to investigate the impacts of different mutations on muscle tissue and to better test treatments. They could also be used as part of regenerative medicine therapies, to restore muscle cells in patients.
Autres résumés
Type: plain-language-summary
(eng)
Muscular dystrophies are a group of inherited genetic diseases characterised by progressive muscle weakness. They lead to disability or even death, and no cure exists against these conditions. Advances in genome sequencing have identified many mutations that underly muscular dystrophies, opening the door to new therapies that could repair incorrect genes or rebuild damaged muscles. However, testing these ideas requires better ways to recreate human muscular dystrophy in the laboratory. One strategy for modelling muscular dystrophy involves coaxing skin or other cells from an individual into becoming ‘induced pluripotent stem cells’; these can then mature to form almost any adult cell in the body, including muscles. However, this approach does not usually create myoblasts, the ‘precursor’ cells that specifically mature into muscle during development. This limits investigations into how disease-causing mutations impact muscle formation early on. As a response, Guo et al. developed a two-step protocol of muscle maturation followed by stem cell growth selection to isolate and grow ‘induced myoblasts’ from induced pluripotent stem cells taken from healthy volunteers and muscular dystrophy patients. These induced myoblasts can both make more of themselves and become muscle, allowing Guo et al. to model three different types of muscular dystrophy. These myoblasts also behave as stem cells when grafted inside adult mouse muscles: some formed human muscle tissue while others remained as precursor cells, which could then respond to muscle injury and start repair. The induced myoblasts developed by Guo et al. will enable scientists to investigate the impacts of different mutations on muscle tissue and to better test treatments. They could also be used as part of regenerative medicine therapies, to restore muscle cells in patients.
Identifiants
pubmed: 35076017
doi: 10.7554/eLife.70341
pii: 70341
pmc: PMC8789283
doi:
pii:
Substances chimiques
Dux4 protein, mouse
0
Homeodomain Proteins
0
PAX3 Transcription Factor
0
Pax3 protein, mouse
138016-91-8
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NICHD NIH HHS
ID : P50 HD060848
Pays : United States
Organisme : NICHD NIH HHS
ID : R37 HD007796
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD060848
Pays : United States
Informations de copyright
© 2022, Guo et al.
Déclaration de conflit d'intérêts
DG Co inventor on "Microhomology Mediated Repair Of Microduplication Gene Mutations" (17/051,632) and "Methods And Compositions For Treatment Of Muscle Disease With iPSC-Induced Human Skeletal Muscle Stem Cells", KD, MS, JY Co-inventor on "Methods And Compositions For Treatment Of Muscle Disease With iPSC-Induced Human Skeletal Muscle Stem Cells", JC Co-inventor on "Methods And Compositions For Treatment Of Muscle Disease With iPSC-Induced Human Skeletal Muscle Stem Cells" and "Microhomology Mediated Repair Of Microduplication Gene Mutations" (17/051,632), ZM, HZ, AB, KW, RM No competing interests declared, AR, MB Was affiliated with Genea BioCells. This author has no financial interests to declare, AK Was a formerly affiliated with Genea BioCells. The author has no financial interests to declare, OK Co-inventor on "Molecular diagnosis of FSHD by epigenetic signature" (US10870886B2) and "Microhomology Mediated Repair Of Microduplication Gene Mutations" (17/051,632) and "Methods And Compositions For Treatment Of Muscle Disease With iPSC-Induced Human Skeletal Muscle Stem Cells", LH Co-inventor on "Methods And Compositions For Treatment Of Muscle Disease with iPSC-Induced Human Skeletal Muscle Stem Cells", CE Co-inventor on "Microhomology Mediated Repair Of Microduplication Gene Mutations" (17/051,632) and "Methods And Compositions For Treatment Of Muscle Disease With iPSC-Induced Human Skeletal Muscle Stem Cells"
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