Single-cell transcriptomics reveals a conserved embryonic progenitor in different human cancers

Khozyainova, A.; Subrakova, V.; Menyailo, M.; Zhigalina, D.; Kireeva, T.; Galiakberova, A.; Berestovoy, M.; Kopantseva, E.; Korobeynikova, A.; Dashinimaev, E.; Loos, D.; Tretyakova, M.; Bokova, U.; Skryabin, N.; Denisov, E.

doi:10.64898/2025.12.11.693590

bioRxiv · 10.64898/2025.12.11.693590

Single-cell transcriptomics reveals a conserved embryonic progenitor in different human cancers

Khozyainova, A.·Subrakova, V.·Menyailo, M.·Zhigalina, D.·Kireeva, T.·Galiakberova, A.·Berestovoy, M.·Kopantseva, E.·Korobeynikova, A.·Dashinimaev, E.·Loos, D.·Tretyakova, M.·Bokova, U.·Skryabin, N.·Denisov, E.

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Abstract

Cellular plasticity, a critical feature of embryonic development, is often reactivated in cancer, enabling tumor cells to acquire stem-like properties and facilitate uncontrolled growth. This study compares cellular plasticity in cancer and early human development by integrating single-cell data from three cancers and embryoid bodies. The analysis identifies a shared, highly proliferative progenitor-like state, driven by an E2F-TFDP transcriptional axis and enriched in key cell-cycle regulators UBE2C, TOP2A, BIRC5, and NUSAP1. Functionally linked to cell-cycle progression and DNA repair, this state acts as a lineage hub within tumors. Spatial transcriptomics revealed that this state is enriched in lung adenocarcinoma and in lung tissue with basal cell hyperplasia, a potential precursor to squamous cell carcinoma. Validation across eight cancer types demonstrates a prevalence of this program in tumors versus normal cells. Collectively, these findings define a conserved mechanism of tumor plasticity with potential for early detection and targeted therapy. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/693590v2_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@d8d8fborg.highwire.dtl.DTLVardef@8d5cb7org.highwire.dtl.DTLVardef@c1f3b0org.highwire.dtl.DTLVardef@165af61_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Khozyainova, A., Subrakova, V., Menyailo, M., Zhigalina, D., Kireeva, T., Galiakberova, A., Berestovoy, M., Kopantseva, E., Korobeynikova, A., Dashinimaev, E., Loos, D., Tretyakova, M., Bokova, U., Skryabin, N., Denisov, E.. 2025-12-13. Single-cell transcriptomics reveals a conserved embryonic progenitor in different human cancers. https://doi.org/10.64898/2025.12.11.693590

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