Endothelial Cell Cycle Control Enables Vascular Specification in the Developing Embryo 24 views

Endothelial cells, which line all blood vessels, are essential for forming and maintaining the circulatory system during development and throughout life. Proper differentiation and specification of the endothelium into arterial, venous, and capillary subtypes is critical for establishing a functional vascular network, yet the mechanisms that guide these early fate decisions remain incompletely understood. Our work identifies cell cycle state as a key determinant of endothelial specification. We found that distinct phases of G1, early and late G1, enrich for venous and arterial subtypes, respectively, even before the onset of blood flow. Moreover, disruption of cell cycle control in the embryo, through endothelial-specific deletion of the cell cycle inhibitor p27 (CDKN1B), impairs arterial-venous specification and vascular development. While the molecular regulators that control G1 sub-states and thus endothelial identity are still unknown, our preliminary studies suggest that novel candidate genes Flrt2 and Unc5b may act as upstream effectors of cell cycle, offering new avenues for dissecting the intersection between cell cycle regulation and endothelial fate. Together, these findings position cell cycle control as a conserved and intrinsic mechanism guiding vascular specification during embryogenesis and offers promising novel avenues for therapeutic treatments for conditions in which vascular identity is dysregulated.

PHD (Doctor of Philosophy)

Vascular Development; Embryonic Development ; Endothelial Specification; Cell Cycle; p27; Unc5b; Vasculogenesis; RNA sequencing; single-cell RNA sequencing; Flrt2

English

2025-10-31