Academic Journal
CRISPR gene editing in pluripotent stem cells reveals the function of MBNL proteins during human in vitro myogenesis
| العنوان: | CRISPR gene editing in pluripotent stem cells reveals the function of MBNL proteins during human in vitro myogenesis |
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| المؤلفون: | Mérien, Antoine, Tahraoui-Bories, Julie, Cailleret, Michel, Dupont, Jean-Baptiste, Leteur, Céline, Polentes, Jérôme, Carteron, Alexandre, Polvèche, Hélène, Concordet, Jean-Paul, Pinset, Christian, Jarrige, Margot, Furling, Denis, Martinat, Cécile |
| المساهمون: | Institut des cellules souches pour le traitement et l'étude des maladies monogéniques (I-STEM), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, Structure et Instabilité des Génomes (STRING), Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), ANR-16-CE17-0018,SEDUCE,utilisation des cellules souches pour identifier des composés thérapeutiques visant les anomalies de splice(2016) |
| المصدر: | ISSN: 0964-6906. |
| بيانات النشر: | HAL CCSD Oxford University Press (OUP) |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] |
| الوصف: | International audience ; Alternative splicing has emerged as a fundamental mechanism for the spatiotemporal control of development. A better understanding of how this mechanism is regulated has the potential not only to elucidate fundamental biological principles, but also to decipher pathological mechanisms implicated in diseases where normal splicing networks are misregulated. Here, we took advantage of human pluripotent stem cells to decipher during human myogenesis the role of muscleblind-like (MBNL) proteins, a family of tissue-specific splicing regulators whose loss of function is associated with myotonic dystrophy type 1 (DM1), an inherited neuromuscular disease. Thanks to the CRISPR/Cas9 technology, we generated human-induced pluripotent stem cells (hiPSCs) depleted in MBNL proteins and evaluated the consequences of their losses on the generation of skeletal muscle cells. Our results suggested that MBNL proteins are required for the late myogenic maturation. In addition, loss of MBNL1 and MBNL2 recapitulated the main features of DM1 observed in hiPSC-derived skeletal muscle cells. Comparative transcriptomic analyses also revealed the muscle-related processes regulated by these proteins that are commonly misregulated in DM1. Together, our study reveals the temporal requirement of MBNL proteins in human myogenesis and should facilitate the identification of new therapeutic strategies capable to cope with the loss of function of these MBNL proteins. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/34312665; hal-03830948; https://hal.science/hal-03830948; https://hal.science/hal-03830948/document; https://hal.science/hal-03830948/file/2022%20HMG.pdf; PUBMED: 34312665; PUBMEDCENTRAL: PMC8682758 |
| DOI: | 10.1093/hmg/ddab218 |
| الاتاحة: | https://hal.science/hal-03830948 https://hal.science/hal-03830948/document https://hal.science/hal-03830948/file/2022%20HMG.pdf https://doi.org/10.1093/hmg/ddab218 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.D214833C |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/hmg/ddab218 |
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