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The DLX2-LAP2α axis licenses ectomesenchymal specification by unlocking chromatin barriers for craniofacial regeneration [scRNA-seq]

GSE297347 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2025/12/08 Platform GPL24247
Summary
The ectomesenchyme generates much of the craniofacial skeleton, sutures, and diverse connective tissues in the mammalian head, yet its derivation from embryonic stem cells (ESCs) and the underlying molecular drivers remain poorly defined. Here, we identified Dlx2 as a key regulator that efficiently directed murine ESCs towards Msx1+ ectomesenchyme, recapitulating the developmental trajectory. These Msx1+ progenitors expressed classical craniofacial markers and retained robust osteochondral bipotency in vitro and in vivo. Mechanistically, DLX2 utilized a lamina-associated polypeptide 2 (LAP2)-dependent nuclear chaperoning system, engaging LAP2α via a 38-amino-acid homeodomain motif to interact with nucleosomes, thereby opening chromatin and activating a craniofacial ectomesenchymal gene network. Disrupting DLX2-LAP2α interaction or silencing Dlx2 targets largely diminished ectomesenchymal differentiation. Our findings established DLX2 as a pioneer factor in ectomesenchyme specification, offering insights into craniofacial development and stem cell engineering.
Published in
DLX2 acts as a pioneer factor and drives Msx1(+) ectomesenchyme formation from embryonic stem cells
Zhang Z, Xu Z, Hu H et al. · Science advances 2026 · PMID 41533791 · doi:10.1126/sciadv.aea0685
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Direct links to NCBI, no account and no request form: the whole study as GSE297347_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 4 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1259423 and SRA study SRP584740. Searching any of these in the dataset finder brings you back here.

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