Hematopoietic stem and progenitor cells (HSPCs) are a subset population of multi-potent cells with self-renewal capability and differentiation into all lineages of blood cells. HSPCs arise from the ventral wall of embryonic dorsal aorta, the hemogenic endothelium in the aorta-gonad-mesonephros (AGM) region, tightly controlled by epigenetic, transcriptional, and signaling networks. However, how developmental hemogenic endothelium performs cell fate surveillances during HSPC emergence and efficiently eliminates them to avoid abnormal hematopoiesis remains elusive.We revealed that Hoxb7a-mediated repression of cdkn2a/b is selectively relieved in hemogenic endothelium, enabling the elimination of defective HSPCs carrying impaired CTCF during zebrafish embryogenesis. These findings identify the CTCF–Hoxb7a–Cdkn2a/b axis as a permissive regulatory pathway in HSPC fate determination. 

DOI: https://doi.org/10.1016/j.jgg.2024.06.001