Pluripotent stem cell-derived skeletal muscle fibers preferentially express myosin heavy-chain isoforms associated with slow and oxidative muscles

Tania Incitti, Alessandro Magli, Alessandro Magli, Asher Jenkins, Karena Lin, Ami Yamamoto, Rita C.R. Perlingeiro, Rita C.R. Perlingeiro

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Skeletal muscle function is essential for health, and it depends on the proper activity of myofibers and their innervating motor neurons. Each adult muscle is composed of different types of myofibers with distinct contractile and metabolic characteristics. The proper balance of myofiber types is disrupted in most muscle degenerative disorders, representing another factor compromising muscle function. One promising therapeutic approach for the treatment of these diseases is cell replacement based on the targeted differentiation of pluripotent stem cells (PSCs) towards the myogenic lineage. We have previously shown that transient induction of Pax3 or Pax7 in PSCs allows for the generation of skeletal myogenic progenitors endowed with myogenic regenerative potential, but whether they contribute to different fiber types remains unknown. Results: Here, we investigate the fiber type composition of mouse PSC-derived myofibers upon their transplantation into dystrophic and non-dystrophic mice. Our data reveal that PSC-derived myofibers express slow and oxidative myosin heavy-chain isoforms, along with developmental myosins, regardless of the recipient background. Furthermore, transplantation of the mononuclear cell fraction re-isolated from primary grafts into secondary recipients results in myofibers that maintain preferential expression of slow and oxidative myosin heavy-chain isoforms but no longer express developmental myosins, thus indicating postnatal composition. Conclusions: Considering oxidative fibers are commonly spared in the context of dystrophic pathogenesis, this feature of PSC-derived myofibers could be advantageous for therapeutic applications.

Original languageEnglish (US)
Article number17
JournalSkeletal muscle
Volume10
Issue number1
DOIs
StatePublished - Jun 3 2020

Bibliographical note

Funding Information:
This project was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, R01 AR055299 and R01 AR071439 (R.C.R.P.).

Keywords

  • Engraftment
  • Fast
  • Fiber types
  • Muscle stem cell
  • Myofibers
  • Pax3
  • Pax7
  • Pluripotent stem cells (PSC)
  • Skeletal myogenesis
  • Slow

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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