从一名患有乌利希先天性肌营养不良且COL6A1基因携带致病性突变的患者身上生成了人诱导多能干细胞系（CRICKi021-A）。

Generation of a human induced pluripotent stem cell line (CRICKi021-A) from a patient with Ullrich congenital muscular dystrophy carrying a pathogenic mutation in the COL6A1 gene.

作者信息

Jiang Yunsong, Devito Liani G, Muntoni Francesco, Healy Lyn, Tedesco Francesco Saverio

机构信息

Department of Cell and Developmental Biology, University College London, London WC1E 6DE, UK; Stem Cells and Neuromuscular Regeneration Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.

Human Embryo and Stem Cell Unit, The Francis Crick Institute, London, UK.

出版信息

Stem Cell Res. 2025 Mar;83:103648. doi: 10.1016/j.scr.2024.103648. Epub 2024 Dec 30.

DOI:10.1016/j.scr.2024.103648

PMID:39764974

Abstract

Ullrich congenital muscular dystrophy (UCMD) represents the most severe subtype of collagen VI-related dystrophies (COL6-RDs), a spectrum of rare extracellular matrix disorders affecting skeletal muscle and connective tissue. Here, we generated an induced pluripotent stem cell (iPSC) line (CRICKi021-A) from a UCMD patient with de novo dominant-negative mutation in COL6A1 gene by reprogramming dermal fibroblasts using a non-integrating mRNA-based protocol. The resulting human iPSCs displayed normal morphology, expressed pluripotency-associated markers and differentiated into the three germ layers. This new COL6A1-mutant iPSC line can be employed for disease modelling and for investigating potential therapies for COL6-RDs.

摘要

乌尔里希先天性肌营养不良症（UCMD）是与VI型胶原蛋白相关的肌营养不良症（COL6-RDs）中最严重的亚型，这是一系列影响骨骼肌和结缔组织的罕见细胞外基质疾病。在此，我们通过使用基于非整合mRNA的方案对皮肤成纤维细胞进行重编程，从一名COL6A1基因发生新生显性负性突变的UCMD患者中生成了诱导多能干细胞（iPSC）系（CRICKi021-A）。所得的人iPSC表现出正常形态，表达多能性相关标志物，并分化为三个胚层。这个新的COL6A1突变iPSC系可用于疾病建模以及研究COL6-RDs的潜在治疗方法。