Hemogenic and aortic endothelium arise from a common hemogenic angioblast precursor and are specified by the Etv2 dosage

Abstract

Significance Hematopoietic stem cells (HSCs) are generated from specialized endothelial cells, called hemogenic endothelial cells (HECs). It has been debated whether HECs and non–HSC-forming conventional endothelial cells (cECs) arise from a common precursor or represent distinct lineages. Moreover, the molecular basis underlying their distinct fate determination is poorly understood. We use photoconvertible labeling, time-lapse imaging, and single-cell RNA-sequencing analysis to trace the lineage of HECs. We discovered that HECs and cECs arise from a common hemogenic angioblast precursor, and their distinct fate is determined by high or low dosage of Etv2, respectively. Our results illuminate the lineage origin and a mechanism on the fate determination of HECs, which may enhance the understanding on the ontogeny of HECs in vertebrates.

Vascular Progenitor Cells: From Cancer to Tissue Repair

“…Subsequently, hemogenic angioblasts are thought to migrate within the fetal liver and fetal BM as these tissues develop. Recently, Zhao et al [ 33 ], using photoconvertible labeling, time-lapse imaging and a single-cell RNA-sequencing analysis in a zebrafish model, found that HE and ECs arise from a common flk1+ precursor, which they refer to as hemogenic angioblasts, and their distinct fate is regulated by ETS transcription factors Etv2. Interestingly, Etv2 has been found to be involved in tumor angiogenesis [ 34 ].…”

Clonal Hematopoiesis: Role in Hematologic Non-Hematologic

“…Recent studies carried out in zebrafish embryos suggest that both hemogenic endothelium and aortic endothelium originated from a common angioblast precursor; this angioblast precursor generates arterial ECs and HECs: these cells display a spatial separation in the dorsal aorta where most ECs are in the floor and most HECs in the roof. 7 The specification of ECs or HECs from the precursor angioblasts is modulated by ETV2 levels through differential regulation of Fli1a, Notch, and Sclβ. 7 In addition, enforced RUNX1 expression in ECs promotes the transition to HECs.…”

“… 7 The specification of ECs or HECs from the precursor angioblasts is modulated by ETV2 levels through differential regulation of Fli1a, Notch, and Sclβ. 7 In addition, enforced RUNX1 expression in ECs promotes the transition to HECs. 7 …”

“…7 The specification of ECs or HECs from the precursor angioblasts is modulated by ETV2 levels through differential regulation of Fli1a, Notch, and Sclβ. 7 In addition, enforced RUNX1 expression in ECs promotes the transition to HECs. 7 The process through which HE generates hematopoietic stem/progenitor cells is an endothelial to hematopoietic transition.…”

“…7 In addition, enforced RUNX1 expression in ECs promotes the transition to HECs. 7 The process through which HE generates hematopoietic stem/progenitor cells is an endothelial to hematopoietic transition. Intra-aortic hematopoietic clusters (IAHCs) contain immature HSCs, HSCs, and committed progenitors.…”