Direct reprogramming of urine-derived cells with inducible MyoD for modeling human muscle disease

Ellis Y. Kim, Patrick Page, Lisa M. Dellefave-Castillo, Elizabeth M. McNally*, Eugene J. Wyatt

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Background: Cellular models of muscle disease are taking on increasing importance with the large number of genes and mutations implicated in causing myopathies and the concomitant need to test personalized therapies. Developing cell models relies on having an easily obtained source of cells, and if the cells are not derived from muscle itself, a robust reprogramming process is needed. Fibroblasts are a human cell source that works well for the generation of induced pluripotent stem cells, which can then be differentiated into cardiomyocyte lineages, and with less efficiency, skeletal muscle-like lineages. Alternatively, direct reprogramming with the transcription factor MyoD has been used to generate myotubes from cultured human fibroblasts. Although useful, fibroblasts require a skin biopsy to obtain and this can limit their access, especially from pediatric populations. Results: We now demonstrate that direct reprogramming of urine-derived cells is a highly efficient and reproducible process that can be used to establish human myogenic cells. We show that this method can be applied to urine cells derived from normal individuals as well as those with muscle diseases. Furthermore, we show that urine-derived cells can be edited using CRISPR/Cas9 technology. Conclusions: With progress in understanding the molecular etiology of human muscle diseases, having a readily available, noninvasive source of cells from which to generate muscle-like cells is highly useful.

Original languageEnglish (US)
Article number32
JournalSkeletal Muscle
Volume6
Issue number1
DOIs
StatePublished - Sep 15 2016

Keywords

  • CRISPR
  • Muscular dystrophy
  • MyoD
  • Myotubes
  • Reprogramming
  • Urine cells

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Direct reprogramming of urine-derived cells with inducible MyoD for modeling human muscle disease'. Together they form a unique fingerprint.

Cite this