![]() ![]() “This unbiased approach led us to uncover, for the first time, a maternal factor called negative elongation factor A (NELFA) that is involved in totipotent gene expression,” Tee explained. Using a hierarchical clustering algorithm, the researchers were able to identify stage-specific gene signatures, allowing them to focus their attention on genes expressed at the two-cell stage of embryonic development. Tee’s team first analyzed the complete gene expression profiles, or transcriptomes, of pre-implantation mouse embryos at various development stages. “In this study, we found that we can activate the totipotent state simply by tweaking the gene expression and metabolic programs of ESCs.” “Totipotent stem cells are the most versatile of the stem cell types,” said Wee-Wei Tee, a Principal Investigator at A*STAR's Institute of Molecular and Cell Biology (IMCB). The classification of totipotency is therefore reserved strictly for cells formed during the earliest stages of embryonic development (the zygote and two- to four-cell stages). By this definition, even embryonic stem cells (ESCs) are not totipotent. However, these iPSCs are not totipotent-they are unable to form the placenta. These reprogrammed cells, known as induced pluripotent stem cells (iPSCs), regain the ability to differentiate into a range of cell types in the body. The 2012 Nobel Prize in Physiology and Medicine was jointly awarded to Shinya Yamanaka and John Gurdon for their discovery that mature cells can be reprogrammed to take on a stem-cell-like state. Modifying how embryonic stem cells use sugar can switch them into a totipotent state, A*STAR researchers say.
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