CECS, I-Stem, AFM, Evry Cedex, France.
Biochem Soc Trans. 2011 Dec;39(6):1775-9. doi: 10.1042/BST20110659.
Progeria, also known as HGPS (Hutchinson-Gilford progeria syndrome), is a rare fatal genetic disease characterized by an appearance of accelerated aging in children. This syndrome is typically caused by mutations in codon 608 (C1804T) of the gene encoding lamins A and C, LMNA, leading to the production of a truncated form of the protein called progerin. Owing to their unique potential to self-renew and to differentiate into any cell types of the organism, pluripotent stem cells offer a unique tool to study molecular and cellular mechanisms related to this global and systemic disease. Recent studies have exploited this potential by generating human induced pluripotent stem cells from HGPS patients' fibroblasts displaying several phenotypic defects characteristic of HGPS such as nuclear abnormalities, progerin expression, altered DNA-repair mechanisms and premature senescence. Altogether, these findings provide new insights on the use of pluripotent stem cells for pathological modelling and may open original therapeutic perspectives for diseases that lack pre-clinical in vitro human models, such as HGPS.
早衰症，又称 HGPS（欣斯丁格-吉尔福德早衰症候群），是一种罕见的致命遗传性疾病，其特征是儿童出现加速衰老的表现。该综合征通常由编码核纤层蛋白 A 和 C 的基因（LMNA）第 608 密码子（C1804T）的突变引起，导致截短形式的蛋白 progerin 的产生。由于其独特的自我更新和分化为生物体任何细胞类型的能力，多能干细胞为研究与这种全身性疾病相关的分子和细胞机制提供了独特的工具。最近的研究利用源自具有 HGPS 几种表型缺陷的患者成纤维细胞的人诱导多能干细胞来实现这一潜能，这些缺陷包括核异常、progerin 表达、DNA 修复机制改变和过早衰老。总之，这些发现为多能干细胞在病理性建模中的应用提供了新的见解，并可能为缺乏临床前体外人类模型的疾病（如 HGPS）开辟新的治疗前景。
