Possible involvement of zinc transporter ZIP13 in myogenic differentiation
Abstract Ehlers–Danlos syndrome spondylodysplastic type 3 (EDSSPD3, OMIM 612350) is an inherited recessive connective tissue disorder that is caused by loss of function of SLC39A13/ZIP13, a zinc transporter belonging to the Slc39a/ZIP family. We previously reported that patients with EDSSPD3 harbori...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-56912-7 |
| _version_ | 1797209348880990208 |
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| author | Masaki Shoji Takuto Ohashi Saki Nagase Haato Yuri Kenta Ichihashi Teruhisa Takagishi Yuji Nagata Yuki Nomura Ayako Fukunaka Sae Kenjou Hatsuna Miyake Takafumi Hara Emi Yoshigai Yoshio Fujitani Hidetoshi Sakurai Heloísa G. dos Santos Toshiyuki Fukada Takashi Kuzuhara |
| author_facet | Masaki Shoji Takuto Ohashi Saki Nagase Haato Yuri Kenta Ichihashi Teruhisa Takagishi Yuji Nagata Yuki Nomura Ayako Fukunaka Sae Kenjou Hatsuna Miyake Takafumi Hara Emi Yoshigai Yoshio Fujitani Hidetoshi Sakurai Heloísa G. dos Santos Toshiyuki Fukada Takashi Kuzuhara |
| author_sort | Masaki Shoji |
| collection | DOAJ |
| description | Abstract Ehlers–Danlos syndrome spondylodysplastic type 3 (EDSSPD3, OMIM 612350) is an inherited recessive connective tissue disorder that is caused by loss of function of SLC39A13/ZIP13, a zinc transporter belonging to the Slc39a/ZIP family. We previously reported that patients with EDSSPD3 harboring a homozygous loss of function mutation (c.221G > A, p.G64D) in ZIP13 exon 2 (ZIP13 G64D ) suffer from impaired development of bone and connective tissues, and muscular hypotonia. However, whether ZIP13 participates in the early differentiation of these cell types remains unclear. In the present study, we investigated the role of ZIP13 in myogenic differentiation using a murine myoblast cell line (C2C12) as well as patient-derived induced pluripotent stem cells (iPSCs). We found that ZIP13 gene expression was upregulated by myogenic stimulation in C2C12 cells, and its knockdown disrupted myotubular differentiation. Myocytes differentiated from iPSCs derived from patients with EDSSPD3 (EDSSPD3-iPSCs) also exhibited incomplete myogenic differentiation. Such phenotypic abnormalities of EDSSPD3-iPSC-derived myocytes were corrected by genomic editing of the pathogenic ZIP13 G64D mutation. Collectively, our findings suggest the possible involvement of ZIP13 in myogenic differentiation, and that EDSSPD3-iPSCs established herein may be a promising tool to study the molecular basis underlying the clinical features caused by loss of ZIP13 function. |
| first_indexed | 2024-04-24T09:53:17Z |
| format | Article |
| id | doaj.art-66db52930fec4ff4bbbebbc1c0f96d83 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-24T09:53:17Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
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| spelling | doaj.art-66db52930fec4ff4bbbebbc1c0f96d832024-04-14T11:17:10ZengNature PortfolioScientific Reports2045-23222024-04-0114111510.1038/s41598-024-56912-7Possible involvement of zinc transporter ZIP13 in myogenic differentiationMasaki Shoji0Takuto Ohashi1Saki Nagase2Haato Yuri3Kenta Ichihashi4Teruhisa Takagishi5Yuji Nagata6Yuki Nomura7Ayako Fukunaka8Sae Kenjou9Hatsuna Miyake10Takafumi Hara11Emi Yoshigai12Yoshio Fujitani13Hidetoshi Sakurai14Heloísa G. dos Santos15Toshiyuki Fukada16Takashi Kuzuhara17Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri UniversityLaboratory of Molecular and Cellular Physiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri UniversityLaboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri UniversityLaboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri UniversityLaboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri UniversityLaboratory of Molecular and Cellular Physiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri UniversityLaboratory of Molecular and Cellular Physiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri UniversityLaboratory of Molecular and Cellular Physiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri UniversityLaboratory of Developmental Biology and Metabolism, Institute for Molecular and Cellular Regulation, Gunma UniversityLaboratory of Molecular and Cellular Physiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri UniversityLaboratory of Molecular and Cellular Physiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri UniversityLaboratory of Molecular and Cellular Physiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri UniversityLaboratory of Molecular and Cellular Physiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri UniversityLaboratory of Developmental Biology and Metabolism, Institute for Molecular and Cellular Regulation, Gunma UniversityCenter for iPS Cell Research and Application (CiRA), Kyoto UniversityServiço Genética Médica, Hospital S. MariaLaboratory of Molecular and Cellular Physiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri UniversityLaboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri UniversityAbstract Ehlers–Danlos syndrome spondylodysplastic type 3 (EDSSPD3, OMIM 612350) is an inherited recessive connective tissue disorder that is caused by loss of function of SLC39A13/ZIP13, a zinc transporter belonging to the Slc39a/ZIP family. We previously reported that patients with EDSSPD3 harboring a homozygous loss of function mutation (c.221G > A, p.G64D) in ZIP13 exon 2 (ZIP13 G64D ) suffer from impaired development of bone and connective tissues, and muscular hypotonia. However, whether ZIP13 participates in the early differentiation of these cell types remains unclear. In the present study, we investigated the role of ZIP13 in myogenic differentiation using a murine myoblast cell line (C2C12) as well as patient-derived induced pluripotent stem cells (iPSCs). We found that ZIP13 gene expression was upregulated by myogenic stimulation in C2C12 cells, and its knockdown disrupted myotubular differentiation. Myocytes differentiated from iPSCs derived from patients with EDSSPD3 (EDSSPD3-iPSCs) also exhibited incomplete myogenic differentiation. Such phenotypic abnormalities of EDSSPD3-iPSC-derived myocytes were corrected by genomic editing of the pathogenic ZIP13 G64D mutation. Collectively, our findings suggest the possible involvement of ZIP13 in myogenic differentiation, and that EDSSPD3-iPSCs established herein may be a promising tool to study the molecular basis underlying the clinical features caused by loss of ZIP13 function.https://doi.org/10.1038/s41598-024-56912-7 |
| spellingShingle | Masaki Shoji Takuto Ohashi Saki Nagase Haato Yuri Kenta Ichihashi Teruhisa Takagishi Yuji Nagata Yuki Nomura Ayako Fukunaka Sae Kenjou Hatsuna Miyake Takafumi Hara Emi Yoshigai Yoshio Fujitani Hidetoshi Sakurai Heloísa G. dos Santos Toshiyuki Fukada Takashi Kuzuhara Possible involvement of zinc transporter ZIP13 in myogenic differentiation Scientific Reports |
| title | Possible involvement of zinc transporter ZIP13 in myogenic differentiation |
| title_full | Possible involvement of zinc transporter ZIP13 in myogenic differentiation |
| title_fullStr | Possible involvement of zinc transporter ZIP13 in myogenic differentiation |
| title_full_unstemmed | Possible involvement of zinc transporter ZIP13 in myogenic differentiation |
| title_short | Possible involvement of zinc transporter ZIP13 in myogenic differentiation |
| title_sort | possible involvement of zinc transporter zip13 in myogenic differentiation |
| url | https://doi.org/10.1038/s41598-024-56912-7 |
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