Marginal zone B-cell dysfunction in ALPS.

in our understanding of hemogenic endothelium induction, many questions remain. ncor2 is expressed throughout the aorta and controls expression of arterial markers throughout the vessel, yet loss of ncor2 only affects hemogenic endothelial formation. What other factors restrict the function of ncor2 within the presumptive hemogenic endothelial cells? Does ncor2 regulate expression of c-fos, vegfd, or Notch targets directly by binding to cell-type specific regulatory elements within these genes? How does ncor2, c-fos, or vegfd alter Notch signaling? vegfd is a prolymphangiogenic molecule, so could the effects observed with vegfd overexpression result from changes to lymphatic vessel formation? Are lymphatic vessel formation and HSPC emergence coordinated? Although lymphatic endothelial cells are derived from venous endothelial cells and not arterial cells, there is evidence that lymphangiogenic factors might have a supportive role for hematopoietic progenitors during development. Could these endothelial fate changes alter the HSPC niche? The work fromWei et al provides novel insight into the delicate balance of endothelial and hematopoietic fate choices during development, offering new directions in the quest to generate functional blood stem cells in vitro for transplantation therapies. Conflict-of-interest disclosure: The author declares no competing financial interests. n