Human embryonic stem cells as a model for studying epigenetic regulation during early development.
In order to exploit the exceptional potential of human embryonic stem cells (hESCs) in cell-replacement therapies, the genetic and epigenetic factors controlling early human development must be better defined. Limitations in human embryonic material restrict the scale of studies that can be performed, and therefore an in vitro model in which to study epigenetic regulation in human preimplantation cell types would be desirable. HESCs could provide such a model, but since they are derived from a stage in mammalian development when the genome is undergoing global epigenetic remodelling, it is unclear whether their epigenetic status would be stable or subject to variation. Herein, we discuss recent work that examines allele-specific imprinted gene expression and methylation patterns, thereby demonstrating that hESCs maintain a substantial degree of epigenetic stability during culture. Therefore, we suggest that hESCs could provide a model for studying epigenetic regulation during the early stages of human cellular pluripotency and differentiation. Furthermore, we propose specific experiments using such a model to address important questions pertaining to epigenetic mechanisms of certain human disorders.
Rugg-Gunn
Peter J
PJ
Department of Surgery, Cambridge Institute for Medical Research, UK. pjr36@cam.ac.uk
Ferguson-Smith
Anne C
AC
Pedersen
Roger A
RA
D000818:Animals; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D013997:Time Factors