In the spotlight: the role of TGFbeta signalling in haematopoietic stem and progenitor cell emergence

Abstract

Haematopoietic stem and progenitor cells (HSPCs) sustain haematopoiesis by generating precise numbers of mature blood cells throughout the lifetime of an individual. In vertebrates, HSPCs arise during embryonic development from a specialised endothelial cell population, the haemogenic endothelium (HE). Signalling by the Transforming Growth Factor Beta (TGFbeta) pathway is key to regulate haematopoiesis in the adult bone marrow, but evidence for a role in the formation of HSPCs has only recently started to emerge. In this review, we examine recent work in various model systems that demonstrate a key role for TGFbeta signalling in HSPC emergence from the HE. The current evidence underpins two seemingly contradictory views of TGFbeta function: as a negative regulator of HSPCs by limiting haematopoietic output from HE, and as a positive regulator, by programming the HE towards the haematopoietic fate. Understanding how to modulate the requirement for TGFbeta signalling in HSC emergence may have critical implications for the generation of these cells in vitro for therapeutic use.