Characterization of hiPSC-Derived Muscle Progenitors Reveals Distinctive Markers for Myogenic Cell Purification Toward Cell Therapy

Autor: Takuma Mizusawa, Hidetoshi Sakurai, Mingming Zhao, Mitsuru Sasaki-Honda, Akitsu Hotta, Tatsuya Jonouchi, Antonio Lucena-Cacace, Masahiko Yasuda, Minas Nalbandian, Yoshinori Yoshida
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Transcription
Genetic
Duchenne muscular dystrophy
Cell- and Tissue-Based Therapy
Cell Separation
Muscle Development
Biochemistry
Cell therapy
0302 clinical medicine
surface marker
Genes
Reporter
RNA-Seq
Induced pluripotent stem cell
muscle stem cell
iPSC
biology
Stem Cells
PAX7 Transcription Factor
Cadherins
Cell biology
medicine.anatomical_structure
MYF5
Myogenic Regulatory Factor 5
Dystrophin
CDH13
Induced Pluripotent Stem Cells
Mice
Transgenic
Article
Cell Line
03 medical and health sciences
Genetics
medicine
Animals
Regeneration
Receptor
Fibroblast Growth Factor
Type 4
Progenitor cell
skeletal muscle
Muscle
Skeletal
Base Sequence
Skeletal muscle
Cell Biology
medicine.disease
Transplantation
030104 developmental biology
Gene Expression Regulation
biology.protein
FGFR4
Transcriptome
030217 neurology & neurosurgery
Biomarkers
Developmental Biology
Zdroj: Stem Cell Reports
ISSN: 2213-6711
Popis: Summary The transplantation of muscle progenitor cells (MuPCs) differentiated from human induced pluripotent stem cells (hiPSCs) is a promising approach for treating skeletal muscle diseases such as Duchenne muscular dystrophy (DMD). However, proper purification of the MuPCs before transplantation is essential for clinical application. Here, by using MYF5 hiPSC reporter lines, we identified two markers for myogenic cell purification: CDH13, which purified most of the myogenic cells, and FGFR4, which purified a subset of MuPCs. Cells purified with each of the markers showed high efficiency for regeneration after transplantation and contributed to the restoration of dystrophin expression in DMD-immunodeficient model mice. Moreover, we found that MYF5 regulates CDH13 expression by binding to the promoter regions. These findings suggest that FGFR4 and CDH13 are strong candidates for the purification of hiPSC-derived MuPCs for therapeutical application.
Graphical abstract
Highlights • MYF5 and PAX7 mark different populations of hiPSC-MuPCs • RNA-seq of MYF5+ cells reveals CDH13 and FGFR4 as hiPSC-MuPC markers • CDH13+ and FGFR4+ hiPSC-MuPCs contribute to regeneration in mdx mice • MYF5 regulates CDH13 expression by binding to its promoter region
Proper purification of muscle progenitor cells (MuPCs) is a necessary step to succeed in cell therapy for Duchenne muscular dystrophy. In this paper, Nalbandian and colleagues identify two surface markers (FGFR4 and CDH13) that allow for the efficient separation of MuPCs from non-myogenic cells in hiPSC-muscle progenitor culture. Cells purified with these markers showed improved myogenic and regeneration capacity.
Databáze: OpenAIRE
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