Ader Flavie, Duboscq-Bidot Laetitia, Marteau Sibylle, Hamlin Matthieu, Richard Pascale, Fontaine Vincent, Villard Eric
Sorbonne Université, INSERM, UMR_S 1166, Paris 75013, France; Molecular and Cellular Cardiogenetic and Myogenetic Functional Unit, Hôpital Pitié Salpétrière, DMU BioGem, APHP-Sorbonne Université, Paris, France; Département 3, UP de Biochimie, UFR de Pharmacie, Université de PARIS, Paris, France.
Sorbonne Université, INSERM, UMR_S 1166, Paris 75013, France; APHP, Pitié-Salpêtrière University Hospital, 75013 Paris, France.
Stem Cell Res. 2022 Jan;58:102616. doi: 10.1016/j.scr.2021.102616. Epub 2021 Dec 4.
Loss-of-function (LoF) mutations in FLNC are strongly associated with dilated cardiomyopathy (DCM). Using CRISPR/Cas9 mediated edition in an healthy donor derived iPSC (ICAN-403.3) we subcloned 1 iPSC line harboring LoF mutation in FLNC. All lines are fully pluripotent and isogenic except at edited site where it presents a homozygous (ICAN-FLNC42.1) deletion of splice site leading to skipping of exon 42 traduced into a short filamin form with reduced expression in derived cardiomyocytes. This line would serve for FLNC mutation DCM modeling after differentiation into cardiocytes or beating organoids.
FLNC基因功能丧失（LoF）突变与扩张型心肌病（DCM）密切相关。我们利用CRISPR/Cas9介导的编辑技术，在一个来自健康供体的诱导多能干细胞（ICAN-403.3）中，亚克隆得到了1个在FLNC基因中携带LoF突变的诱导多能干细胞系。除了编辑位点外，所有细胞系均具有完全多能性且为同基因，在编辑位点呈现纯合缺失的剪接位点，导致外显子42跳跃，在分化的心肌细胞中翻译为短的细丝蛋白形式且表达降低。该细胞系在分化为心肌细胞或跳动类器官后，可用于FLNC突变DCM的建模。
