Cellular diversity within embryonic stem cells: pluripotent clonal sublines show distinct differentiation potential

Journal of Cellular and Molecular Medicine

Yannick Martinez²  Frédérique Béna¹  Stefania Gimelli¹  Diderik Tirefort²  Michel Dubois-Dauphin²  Karl-Heinz Krause² 

[1] Service of Genetic Medicine, University of Geneva Hospital, Switzerland;Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland

关键词: embryonic stem cell;    cloning;    differentiation;    neural differentiation;   

DOI  :  10.1111/j.1582-4934.2011.01334.x

来源: Wiley

【 摘 要 】

Abstract

Embryonic stem cells (ESC), derived from the early inner cell mass (ICM), are constituted of theoretically homogeneous pluripotent cells. Our study was designed to test this concept using experimental approaches that allowed characterization of progenies derived from single parental mouse ESC. Flow cytometry analysis showed that a fraction of ESC submitted to neural differentiation generates progenies that escape the desired phenotype. Live imaging of individual cells demonstrated significant variations in the capacity of parental ESC to generate neurons, raising the possibility of clonal diversity among ESC. To further substantiate this hypothesis, clonal sublines from ESC were generated by limit dilution. Transcriptome analysis of undifferentiated sublines showed marked differences in gene expression despite the fact that all clones expressed pluripotency markers. Sublines showed distinct differentiation potential, both in phenotypic differentiation assays and with respect to gene expression in embryoid bodies. Clones generated from another ESC line also showed individualities in their differentiation potential, demonstrating the wider applicability of these findings. Taken together, our observations demonstrate that pluripotent ESC consist of individual cell types with distinct differentiation potentials. These findings identify novel elements for the biological understanding of ESC and provide new tools with a major potential for their future in vitro and in vivo use.

【 授权许可】

Unknown   
© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd