This pattern of Notch pathway gene expression changes is consistent with recent studies suggesting that, although Notch1 is required early for definitive hematopoietic fate, the emergence of HSCs from HE correlates with decreased Notch1 expression, lower overall Notch signal strength, and a requirement for Hes1 in limiting Notch-dependent Gata2 expression6,59–62. Here, HES1 is linked to hereditary elliptocytosis.