HOIL-1L deficiency induces cell cycle alteration which causes immaturity of skeletal muscle and cardiomyocytes

HOIL-1L deficiency was recently reported to be one of the causes of myopathy and dilated cardiomyopathy (DCM). However, the mechanisms by which myopathy and DCM develop have not been clearly elucidated. Here, we sought to elucidate these mechanisms using the murine myoblast cell line C2C12 and disea...

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Published inScientific reports Vol. 14; no. 1; p. 8871
Main Authors Akagi, Kentaro, Baba, Shiro, Fujita, Hiroaki, Fuseya, Yasuhiro, Yoshinaga, Daisuke, Kubota, Hirohito, Kume, Eitaro, Fukumura, Fumiaki, Matsuda, Koichi, Tanaka, Takayuki, Hirata, Takuya, Saito, Megumu K., Iwai, Kazuhiro, Takita, Junko
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 17.04.2024
Nature Publishing Group
Nature Portfolio
Subjects
692/699
692/699/75
Cardiomyocytes
Cardiomyopathy
Cell cycle
Cell differentiation
Cell proliferation
Cytology
Dilated cardiomyopathy
Genes
Heart
Humanities and Social Sciences
Maturation
Medical prognosis
multidisciplinary
Muscle contraction
Musculoskeletal system
Myoblasts
Myopathy
Myotubes
Patients
Pediatrics
Pluripotency
Proteins
Science
Science (multidisciplinary)
Skeletal muscle
Stem cells
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Summary:HOIL-1L deficiency was recently reported to be one of the causes of myopathy and dilated cardiomyopathy (DCM). However, the mechanisms by which myopathy and DCM develop have not been clearly elucidated. Here, we sought to elucidate these mechanisms using the murine myoblast cell line C2C12 and disease-specific human induced pluripotent stem cells (hiPSCs). Myotubes differentiated from HOIL-1L-KO C2C12 cells exhibited deteriorated differentiation and mitotic cell accumulation. CMs differentiated from patient-derived hiPSCs had an abnormal morphology with a larger size and were excessively multinucleated compared with CMs differentiated from control hiPSCs. Further analysis of hiPSC-derived CMs showed that HOIL-1L deficiency caused cell cycle alteration and mitotic cell accumulation. These results demonstrate that abnormal cell maturation possibly contribute to the development of myopathy and DCM. In conclusion, HOIL-1L is an important intrinsic regulator of cell cycle-related myotube and CM maturation and cell proliferation.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-024-57504-1