Small molecule inhibitors promote efficient generation of induced pluripotent stem cells from human skeletal myoblasts.
Human somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by ectopic expression of key transcription factors. iPSCs have been generated from a variety of cell types. However, iPSC induction from human myoblasts has not yet been reported. Human primary skeletal myoblasts can be cultured from diagnostic muscle biopsy specimens, and thousands of lines are frozen and stored in biobanks, and are a valuable source for iPSC-based etiological and pathogenic studies. Our aim was to generate iPSCs from human skeletal myoblasts enriched from muscle biopsy samples. We used retro- or Sendai virus vector-mediated reprogramming of enriched human myoblasts from 7 donors. We show that stable iPSC lines can be generated from human myoblasts at efficiency similar to that of fibroblasts when appropriate media is used, and the efficiency of the feeder-free iPSC generation can be significantly improved by inhibitors of histone deacetylase (sodium butyrate) and TGF-β signaling (SB431542).
Research Programs Unit, Molecular Neurology, Biomedicum Stem Cell Center, University of Helsinki, Helsinki, Finland. ras.trokovic@helsinki.fi
Ras
R
Trokovic
Jere
J
Weltner
Tuula
T
Manninen
Milla
M
Mikkola
Karolina
K
Lundin
Riikka
R
Hämäläinen
Anu
A
Suomalainen
Timo
T
Otonkoski
D000328:Adult; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001549:Benzamides / Q000494:pharmacology*; D020148:Butyric Acid / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003470:Culture Media; D004149:Dioxoles / Q000494:pharmacology*; D005260:Female; D020868:Gene Silencing; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects / Q000502:physiology*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D032448:Myoblasts, Skeletal / Q000502:physiology*; D012190:Retroviridae / Q000235:genetics; D029082:Sendai virus / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013724:Teratoma / Q000473:pathology; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta / Q000502:physiology; D055815:Young Adult
C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D000943:Antigens, Differentiation; D001549:Benzamides; D003470:Culture Media; D004149:Dioxoles; D056572:Histone Deacetylase Inhibitors; D016212:Transforming Growth Factor beta; D020148:Butyric Acid