2026-04-14T05:02:02Zhttps://recercat.cat/oai/request

oai:recercat.cat:2072/4852222025-08-31T18:17:21Zcom_2072_98col_2072_378192

00925njm 22002777a 4500 dc Núñez-Manchón, Judith author Capó, Júlia author Martínez-Piñeiro, Alicia author Juanola, Eduard author Pesovic, Jovan author Mosqueira-Martín, Laura author González-Imaz, Klaudia author Maestre-Mora, P. author Odria, Renato author Savic-Pavicevic, Dusanka author Vallejo-Illarramendi, Ainara author Mamchaoui, Kamel author Bigot, Anne author Mouly, Vicent author Suelves, Mònica author Nogales, Gisela author Universitat Autònoma de Barcelona author 2024 Historically, cellular models have been used as a tool to study myotonic dystrophy type 1 (DM1) and the validation of therapies in said pathology. However, there is a need for in vitro models that represent the clinical heterogeneity observed in patients with DM1 that is lacking in classical models. In this study, we immortalized three DM1 muscle lines derived from patients with different DM1 subtypes and clinical backgrounds and characterized them at the genetic, epigenetic, and molecular levels. All three cell lines display DM1 hallmarks, such as the accumulation of RNA foci, MBNL1 sequestration, splicing alterations, and reduced fusion. In addition, alterations in early myogenic markers, myotube diameter and CTCF1 DNA methylation were also found in DM1 cells. Notably, the new lines show a high level of heterogeneity in both the size of the CTG expansion and the aforementioned molecular alterations. Importantly, these immortalized cells also responded to previously tested therapeutics. Altogether, our results show that these three human DM1 cellular models are suitable to study the pathophysiological heterogeneity of DM1 and to test future therapeutic options. http://hdl.handle.net/2072/485222 Immortalized human myotonic dystrophy type 1 muscle cell lines to address patient heterogeneity