Lamin A/C mutations alter differentiation potential of mesenchymal stem cells |
| |
Authors: | A B Malashicheva A S Zabirnik N A Smolina R I Dmitrieva A A Kostareva |
| |
Institution: | 1. Almazov Federal Heart, Blood, and Endocrinology Centre, St. Petersburg, Russia 2. St. Petersburg State University, St. Petersburg, Russia 3. Karazin Kharkiv National University, Kharkiv, Ukraine 4. Virola Cell Biotechnology Laboratory, Kharkiv, Ukraine
|
| |
Abstract: | Mutations in the lamin A/C gene (LMNA) lead to severe disorders collectively called laminopathies. The mechanisms by which lamin mutations cause the diseases are not clear. Since the mesenchymal lineages, adipose tissue in particular, are mostly affected in laminopathies, the aim of the study was to estimate the effect of LMNA mutations on differentiation of mesenchymal stem cells, adipose tissue stromal cells (ATSCs), into adipose lineages. ATSCs transduced with lentiviral vectors carrying LMNA gene mutations associated with various syndromes (myodystrophy, cardiomyopathy, lipodystrophy, progeroid syndrome) were induced to adipose differentiate. It was found that introduction of genetic constructions with LMNA gene point mutations G465D, R482L, and R527C promote adipogenic differentiation compared to wild-type lamin gene; mutation R471C reduced the differentiation. Introduction of R471C or R527C lamin mutations profoundly increased the expression of adipogenesis markers PPARG, SREBP1, and adipsin. Mutations in A/C lamin gene strongly and variously affect the differentiation of mesenchymal stem cells that probably underlie the pathogenic changes in patients with laminopathies. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|