Molecular and Functional kinetics of mesenchymal stem cells differentiated from patient iPSCs and SCNT-ESCs with premature aging

Abstract

Patient-specific pluripotent stem cells can be generated via nuclear reprogramming with YAMANAKA factors (iPSCs) or by somatic nuclear transfer (SCNT-ESCs). However, molecular and functional features of differentiated cells with different reprogramming mechanism remains to be evaluated. Here, we focused on premature aging HGPS caused by heterozygous C1824T point mutation in LMNA that leading to a detrimental accumulation of progerin, an aberrant form of nuclear structural protein Lamin A. Thus, we generated HGPS patient-specific iPSCs and NT-ESCs, differentiated them to mesenchymal stem cells (MSCs) which can recapitulate aging-related phenotypes and compared these MSCs in normal physiological process and in response to stress. This work builds up stem cell based drug screening platform for premature aging intervention and provides promise for ideal cell therapy in regenerative medicine.