Abstract
A critical aspect of understanding human embryonic stem cell (hESC) differentiation is regulation of protein activity. After all, it is by selectively activating and inhibiting various proteins that cells are able to proliferate and differentiate. One way Nature achieves this is by changing the availability of the metal ions that activate or inhibit existing proteins. An estimated one third of all proteins bind metal ions which play numerous critical cellular roles including as cofactors for enzymatic reactions, structural nuclei for protein folding motifs, and various signaling pathways.We are elucidating the role of metals in the dynamic cellular process of hESC differentiation at a systems level and developing analytical tools applicable to any cellular system in which metal ions play such roles. Combining existing molecular and cell biology approaches with cutting‐edge x‐ray fluorescent capabilities at the APS, we are currently investigating dynamics in metal ion distribution across stem cell colonies upon induction of differentiation, seeking a paradigm for the role of metal ions in developmental biology. We find that cellular zinc levels may serve as a biomarker of differentiation, indirectly correlating with the expression of pluripotency markers.
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