Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we will assume that you are happy to receive all cookies and you will not see this message again. Click 'Find out more' for information on how to change your cookie settings.

Hematopoietic stem cells (HSCs) are self-renewing multipotent stem cells that generate mature blood lineages throughout life. They, together with hematopoietic progenitor cells (collectively known as HSPCs), emerge from hemogenic endothelium in the floor of the embryonic dorsal aorta by an endothelial-to-hematopoietic transition (EHT). Here we demonstrate that transforming growth factor β (TGFβ) is required for HSPC specification and that it regulates the expression of the Notch ligand Jagged1a in endothelial cells prior to EHT, in a striking parallel with the epithelial-to-mesenchymal transition (EMT). The requirement for TGFβ is two fold and sequential: autocrine via Tgfβ1a and Tgfβ1b produced in the endothelial cells themselves, followed by a paracrine input of Tgfβ3 from the notochord, suggesting that the former programs the hemogenic endothelium and the latter drives EHT. Our findings have important implications for the generation of HSPCs from pluripotent cells in vitro.

Original publication

DOI

10.1016/j.devcel.2016.06.024

Type

Journal article

Journal

Dev Cell

Publication Date

22/08/2016

Volume

38

Pages

358 - 370

Keywords

EHT, TGFβ, hematopoietic stem cell, jag1a, notch, zebrafish, Animals, Animals, Genetically Modified, Cell Differentiation, Core Binding Factor Alpha 2 Subunit, Endothelium, Vascular, Epithelial-Mesenchymal Transition, Hematopoietic Stem Cells, Jagged-1 Protein, Morpholinos, Multipotent Stem Cells, Notochord, Signal Transduction, Transforming Growth Factor beta1, Transforming Growth Factor beta2, Transforming Growth Factor beta3, Vascular Endothelial Growth Factor A, Zebrafish, Zebrafish Proteins