A human iPSC model of hutchinson fgilford progeria reveals vascular smooth muscle and mesenchymal stem cell defects (Cell Stem Cell, 2011, 8:31-45)

報告日期: 2011/05/03
報告時間: 16:00/16:50
報告學生: 莊博凱
講評老師: 江美治

Full Text: http://basicmed.med.ncku.edu.tw/admin/up_img/0503-2.pdf

A Human iPSC Model of Hutchinson Gilford Progeria Reveals Vascular Smooth Muscle and Mesenchymal Stem Cell Defects
Cell Stem Cell. 2011 Jan 7;8(1):31-45.
Jinqiu Zhang,Qizhou Lian,Guili Zhu, Fan Zhou, Lin Sui, Cindy Tan, Rafidah Abdul Mutalif, Raju
Navasankari, Yuelin Zhang, Hung-Fat Tse, Colin L. Stewart, and Alan Colman
Date: 2011/05/03 16:00~17:00
Speaker: Po Kai Chuang
Commentator: Jiang, Meei-Jyh, Ph.D.
Hutchinson–Gilford progeria syndrome (HGPS) is a rare and fatalhuman premature ageing disease which depletion of subcutaneous fat to loss of hair and vascular defects due to recurring strokes. HGPS is caused by a single point mutation in the laminA (LMNA) gene, resulting in the generation of progerin, a truncatedsplicingmutant of lamin A, characterized by prematurearteriosclerosis and degeneration of vascular smooth muscle cells(VSMCs) and mesenchymal lineages, including skeletal system and dermis. Heregenerationof inducedpluripotent stemcells (iPSCs) fromfibroblastsobtained from patients with HGPS for providing a powerful new tool to unravel the molecular and physiological mechanisms of premature and normal aging. HGPS-iPSCs show hightestofprogerin, lack the nuclear envelope, andsenescencephenotypes associated with premature ageing. Additionally, this research shows that LMNA expression in patient and control fibroblasts was suppressed by reprogramming. But differentiation of the HGPS-iPSC clones always resulted in expression of lamins A/C, and progerin and functional defects under stress of hypoxia. They propose that, in HGPS patients reveal depletion of the mecenchymal stem cells (MSCs) and VSMCs pools counteractive for alteration differentiated cells lost to progerin effects. Because progerin also accumulates during physiological ageing,this evidence provide in vitro patient-specific ips -based model to studythe pathogenesis of human premature and physiological vascular and mesenchymal lineage tissues ageing.
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