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September 7th, 2025
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University of Helsinki, Faculty of Medicine, Research Programs Unit
developmental biology
bioRxiv

Integrated transcriptomic analysis reveals a metabolically quiescent state and gene expression networks related to intermediate and mature human 8-cell stage embryo resembling cells in vitro

Paloviita, P.Open in Google Scholar•Nykanen, S.Open in Google Scholar•Vuoristo, S.Open in Google Scholar

Human early development is challenging to study due to limited samples and cell numbers. The emergence of 8-cell stage 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 (scRNA-seq) datasets from multiple studies, we integrated data to identify key gene co-expression modules, transposable element (TE) expression, and biological processes recapitulated in 8CLCs. We identified both mature and intermediate 8CLCs, with the Yoshihara and Mazid datasets best representing 8-cell stage embryos. 8CLCs show quiescence in energy and RNA metabolism, regulation of RNA splicing, and ribosome biogenesis, mirroring human 8-cell stage embryos. Our findings underscore the importance of distinguishing mature 8CLCs from partially reprogrammed cell states to improve their use as models for human EGA, in vitro.

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