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Mycn Facilitates Hematopoietic Stem and Progenitor Cell Generation from Endothelial Cells by Inhibiting Adhesion Signaling

ABSTRACT: Hematopoietic stem and progenitor cells (HSPCs) arise from hemogenic endothelial cells (HECs) via the endothelial-to-hematopoietic transition (EHT). As a signature gene of hematopoietic stem cell-primed HECs, Mycn is highly expressed in these cells alongside its paralog, Myc. However, their roles and underlying mechanisms in EHT remain unclear. Here, we demonstrate that endothelial-specific deletion of Mycn, but not Myc, impairs HSPC formation in mouse embryos. Single-cell transcriptomics and functional assays reveal that Mycn deficiency specifically attenuates the HEC-to-HSPC transition but not thereafter. We also establish a mosaic analysis strategy to distinguish Mycn deletion states in mutant embryos, enabling precise characterization. Unlike control HECs that downregulate adhesion signatures during their specification, Mycn-deficient HECs aberrantly upregulate adhesion pathways. Inhibiting focal adhesion kinase, a critical modulator of cell adhesion, rescues HSPC production in Mycn-deficient explant cultures. These findings uncover a regulatory mechanism whereby Mycn promotes HSPC generation from endothelial cells by suppressing adhesion signaling.

ORGANISM(S): Mus musculus

PROVIDER: GSE299909 | GEO | 2026/09/01

REPOSITORIES: GEO

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