PT  - JOURNAL ARTICLE
AU  - Briane Laruy
AU  - Irene Garcia-Gonzalez
AU  - Veronica Casquero-Garcia
AU  - Rui Benedito
TI  - Endothelial-to-hematopoietic transition is induced by Notch glycosylation and upregulation of Mycn
AID  - 10.1101/2020.09.13.295238
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.09.13.295238
4099  - http://biorxiv.org/content/early/2020/09/13/2020.09.13.295238.short
4100  - http://biorxiv.org/content/early/2020/09/13/2020.09.13.295238.full
AB  - A better understanding of the molecular mechanisms driving hematopoietic stem cell (HSC) specification and expansion may enable better pharmacological strategies to produce them in sufficient numbers for transplantation. In the embryo, HSCs arise from a defined subset of arterial endothelial cells (ECs) located in the aorta–gonad–mesonephros (AGM) region that undergo endothelial-to-hematopoietic transition (EHT). Arterialization and HSC development are generally believed to require the action of Notch. Here we show that although Notch activity is initially required for arterialization, it is detrimental to subsequent EHT. Mechanistically, we show that effective EHT depends on a Mfng-induced decrease in Jag1-Notch signaling in hemogenic ECs. This causes upregulation of Mycn, an important metabolic and cell-cycle regulator that we found to be required for EHT. During the subsequent development of hematopoietic lineages, Mycn expression decreases and its function is taken on by the homologous Myc gene.Competing Interest StatementThe authors have declared no competing interest.