BioProject

Metabolic reprogramming plays important roles in embryo development. However, the metabolic network has still not been systematically investigated during the processes. More...

Metabolic reprogramming plays important roles in embryo development. However, the metabolic network has still not been systematically investigated during the processes. In this study, we develop MFE, a metabolites flux estimation tool, to predict metabolite abundances and their regulons, highlighting the role of Fe(II) and its regulon-ISCA2, in the inner cell mass (ICM) of human and mouse blastocysts. By introducing Isca2-/-, Isca2G77S/G77S and Isca2C144S/C144S mice, we find ISCA2 binding with iron, but not Fe-S cluster, is indispensable for mouse peri-implantation development. Mechanistically, nuclear ISCA2 interacts with TET, and Fe(II) is important for the interaction by triggering the enzymatic activity of TET. The partnership safeguards promoters of epiblast-specific genes from hypermethylation and is essential for epiblast development in mouse peri-implantation embryos. The study provides insights into how iron metabolism modulates embryo development, and suggests a manner of Fe(II)-dependentenzymes to achieve activity under physiological conditions. Overall design: RNA-seq, small RNA-seq, EM-seq of mouse Isca2 WT and KO pre-implantation embryos. To collected pre-implantation embryos, Isca2+/- female mouse intraperitoneal with 6.5 international unit of pregnant mares’ serum gonadotropin and, 45 to 47 h later, with 5 IU of human chorionic gonadotropin and crossed to Isca2+/- males. Less...