Integrated transcriptomic analysis reveals metabolic remodeling and gene expression networks related to human 8-cell-stage embryo-like cells

Human early development is challenging to study due to limited samples and cell numbers. The emergence of 8-cell-stage (8C) embryo-like cells (8CLCs) offers new opportunities to understand embryonic genome activation (EGA) in humans. Our research compares and characterizes 8CLCs from various stem cell-based systems to determine how well these models reflect human early embryonic development. Using single-cell RNA sequencing datasets from multiple studies, we integrate data to identify key gene co-expression modules, transposable element expression, and biological processes recapitulated in 8CLCs. We identify both mature and intermediate 8CLCs, with the Yoshihara and Mazid datasets best representing 8C embryos. 8CLCs show remodeling in energy and RNA metabolism, regulation of RNA splicing, and ribosome biogenesis, mirroring human 8C embryos. Our findings underscore the importance of distinguishing mature 8CLCs from partially reprogrammed cell states to improve their use as models for human EGA.