Abstract
The conversion of lysine to glutamate is needed for signaling in all plants and animals. In mouse embryonic stem (mES) cells, and probably their progenitors, endogenous glutamate production and signaling help maintain cellular pluripotency and proliferation, although the source of glutamate is yet to be determined. If the source of glutamate is lysine, then lysine deprivation caused by maternal low-protein diets could alter early embryo development and, consequently, the health of the offspring in adulthood. For these reasons, we measured three pertinent variables in human embryonic stem (hES) cells as a model for the inner cell masses of human blastocysts. We found that RNA encoding the alpha-aminoadipic semialdehyde synthase enzyme, which regulates glutamate production from lysine, was highly expressed in hES cells. Moreover, the mean amount of lysine consumed by hES cells was 50% greater than the mean amount of glutamate they produced, indicating that lysine is likely converted to glutamate in these cells. Finally, hES cells expressed RNA encoding at least two glutamate receptors. Since this may also be the case for hES progenitor cells in blastocysts, further studies are warranted to verify the presence of this signaling process in hES cells and to determine whether lysine deprivation alters early mammalian embryo development.
Highlights
As shown by in vitro studies, amino acids derived from dietary protein are likely to support normal preimplantation embryo development in vivo [1]
Encoding at least two glutamate receptors. Since this may be the case for human embryonic stem (hES) progenitor cells in blastocysts, further studies are warranted to verify the presence of this signaling process in hES cells and to determine whether lysine deprivation alters early mammalian embryo development
Alpha-aminoadipic semialdehyde synthase RNASeq expression decreased to 1/22 of its level in H1 hES cells as these cells differentiated into mesenchymal cells (p < 0.0001), and a similar effect was found for osteogenic, vascular, and neural differentiation (Figure 1; ANOVA, Effect Size = r = 0.999, crucial practical importance, p < 0.0001)
Summary
As shown by in vitro studies, amino acids derived from dietary protein are likely to support normal preimplantation embryo development in vivo [1]. Essential amino acids, including lysine, promote development of blastocysts with more cells in their inner cell masses by increasing the cleavage rate of embryos. Such blastocysts give rise to viable fetuses upon transfer to surrogate mothers more frequently than blastocysts that develop in vitro without essential amino acids [3]. Blastocysts developing in a medium containing essential amino acids produce larger fetuses. While essential amino acids support growth and development as nutrients, they foster signaling in early embryos [1,4,5,6]. Amino acid transport proteins are needed in plasma membranes to regulate the concentrations of essential amino acids in conceptuses, but these transporters can be overwhelmed by altered amino acid availability
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