Primary cilia regulate hematopoietic stem and progenitor cell specification through Notch signaling

Hematopoietic stem and progenitor cells (HSPCs) are capable of producing all mature blood lineages, as well as maintaining the self-renewal ability throughout life. The hairy-like organelle, cilia, are present in most types of vertebrate cells, and play important roles in various biological processes. However, it is unclear whether and how cilia regulate HSPC development in vertebrates. Here, we show that cilia-specific genes, involved in primary cilia formation and signaling transduction, are required for HSPC development, especially at the hemogenic endothelium (HE) specification step in zebrafish embryos. Blocking primary cilia formation or function by genetic or chemical manipulations impaired HSPC development. Mechanistically, we uncover that primary cilia on endothelial cells (ECs) transduce Notch signal to the earliest HE for proper HSPC specification during embryogenesis. Altogether, our findings reveal a pivotal role of endothelial primary cilia in HSPC development, and may shed lights into in vitro directed differentiation of HSPCs.