Abstract
Numerous studies have focused on the transcriptional signatures that underlie the maintenance of embryonic stem cell (ESC) pluripotency. However, it remains unclear whether ESC retain transcriptional aberrations seen in in vitro cultured embryos. Here we report the first global transcriptional profile comparison between ESC generated from either in vitro cultured or in vivo derived primate embryos by microarray analysis. Genes involved in pluripotency, oxygen regulation and the cell cycle were downregulated in rhesus ESC generated from in vitro cultured embryos (in vitro ESC). Significantly, several gene differences are similarly downregulated in preimplantation embryos cultured in vitro, which have been associated with long term developmental consequences and disease predisposition. This data indicates that prior to derivation, embryo quality may influence the molecular signature of ESC lines, and may differentially impact the physiology of cells prior to or following differentiation.
Highlights
Embryonic stem cells (ESC) derived from the inner cell mass (ICM) of preimplantation embryos have the potential to differentiate into any cell type of the three embryonic germ layers
Data suggests that embryonic stem cells may retain a transcriptional memory representative of the environment of the preimplantation embryo from which the cells were derived
In vitro ESC exhibit transcriptional perturbations seen in in vitro cultured embryos, including alterations in markers of pluripotency and differences impacted by oxygen concentration
Summary
Embryonic stem cells (ESC) derived from the inner cell mass (ICM) of preimplantation embryos have the potential to differentiate into any cell type of the three embryonic germ layers. ESC retain the ability to proliferate indefinitely, and maintain pluripotency through conserved regulatory networks; require the provision of various extrinsic factors within the culture environment for continued growth and self-renewal capacity [1,2]. ESC exhibit significant heterogeneity between and within lines, displaying differences in gene expression and differentiation capacity, as well as changes with increasing passage number and culture environment [8,9,10,11], largely attributed to adaptation with long term culture [12,13]. Significant differences have been observed between human ESC lines attributed to differences in derivation techniques [14] and culture conditions [15,16,17]. Very little attention has been paid to other factors which may contribute to the overall normalcy of these cell lines, the quality of the embryo from which a line is derived
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