Abstract
Novel Male DUX4-Inducible Stem Cell Lines for Studying Embryonic Genome Activation
Authors: Kordemets, Katariina; Mikkola, Lea; Danti, Laura; Boskovic, Nina; Katayama, Shintaro; Weltner, Jere; Kere, Juha
Conference name: Awakening the Genome During Developmental Reprogramming: From Embryos to Organoids
Publication year: 2026
Publication's open availability at the time of reporting: No Open Access
Publication channel's open availability : No Open Access publication channel
We have previously demonstrated that inducible DUX4 expression in the female human embryonic stem cell line H9 induces early embryonic genome activation (EGA) like transcriptional programs. However, in order to study sex-dependent differences, comparable male cell lines have to be established. Here, we generated four doxycycline-inducible DUX4 clonal lines from a male hiPSC background and analyzed their transcriptional responses after induction using scRNA-seq. All clones reproducibly formed an iBM-like cluster expressing EGA marker genes, with pseudotime analysis showing a clear separation of the iBM trajectory from other cell states. This reproduces prior observations in the female H9 hESC line, demonstrating conservation of DUX4-driven programs across pluripotent stem cell origin and genetic sex. These XX and XY lines enable future investigation of sex-dependent regulatory dynamics during DUX4-induced cell state transitions.
Keywords:
Embryonic genome activation
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