Cell interactions and cell signaling during hematopoietic development

Abstract

Hematopoiesis is a key process that leads to the formation of all blood cell lineages from a specialized, multipotent cell, named the Hematopoietic Stem Cell (HSC). During development, the embryo produces several waves of hematopoiesis that produce specialized subsets of hematopoietic cells. Tissue interactions and cell signaling play an essential role in developmental hematopoiesis by allowing the formation of hematopoietic and endothelial cells (EC) from the mesoderm in particular in the yolk sac and by instructing the different generations of hematopoietic cells (HC). The embryonic aorta is another site wherein tissue interaction is essential for the production of the first HSCs that is achieved from a specialized subset of hemogenic endothelial cells. This production is tightly time-and space-controlled with the transcription factor Runx1 and the Notch signaling pathway playing a key role in this process and the surrounding tissues controlling the aortic shape and fate. Here we shall briefly review how hemogenic EC differentiate from the mesoderm, how the different aortic components assemble coordinately to establish the dorso-ventral polarity resulting in the initiation of Runx1 expression in hemogenic EC and the initiation of the hematopoietic program through modulation of the NotchRunx1 axis. These data should help elucidate the first steps in HSC commitment and bring further insights into the manipulation of adult HSCs.

Dpp dependent Hematopoietic stem cells give rise to Hh dependent blood progenitors in larval lymph gland of Drosophila

“…Our genetic analyses clearly demonstrate that attenuation of Dpp signaling affects HSCs maintenance in the early lymph gland. This reflects a great degree of similarity to the vertebrate AGM related HSCs that express BMP4 receptor and require BMP4 signaling as the niche signal from the neighboring mesenchyme for their maintenance (Durand et al, 2007; Drevon and Jaffredo, 2014). It has been demonstrated that both the vertebrate AGM and Drosophila cardiogenic mesoderm are specified by identical signals and house blood cell precursors originating from hemangioblasts (Mandal et al, 2004; Choi et al, 1998).…”

Tril targets Smad7 for degradation to allow hematopoietic specification in Xenopus embryos

“…Signals from non-hematopoietic cell niches play an essential role in directing primitive hematopoiesis (Drevon and Jaffredo, 2014). In mouse and chick, hematopoietic mesoderm cannot autonomously differentiate as blood when cultured in isolation, but requires noncell-autonomous signals transmitted from visceral endoderm in order to do so (Belaoussoff et al, 1998;Wilt, 1965).…”

GATA2 regulates Wnt signaling to promote primitive red blood cell fate

“…During vertebrate hematopoiesis, stem cells differentiate along one of the various blood lineages (Drevon and Jaffredo, 2014). The first blood progenitors arise from mesodermal cells that are specified with a hematopoietic fate during gastrulation.…”