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 |
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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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