Abstract
Transforming growth factor beta (TGFbeta) plays an important role in development and maintenance of murine yolk sac vascular development. Targeted deletions of Tgfb1 and other components of this signaling pathway, such as Acvrl1, Tgfbr1 and Tgfbr2, result in abnormal vascular development especially of the yolk sac, leading to embryonic lethality. There are significant differences between murine and primate development that limit interpretation of studies from mouse models. Thus, to examine the role of TGFbeta in early human vascular development we used the model of differentiating human embryonic stem cell-derived embryoid bodies to recapitulate early stages of embryonic development. TGFbeta was applied for different time frames after initiation of embryoid body cultures to assess its effect on differentiation. TGFbeta inhibited the expression of endodermal, endothelial and hematopoietic markers, which contrasts with findings in the mouse in which TGFbeta reduced the level of endodermal markers but increased endothelial marker expression. The inhibition observed was not due to changes in proliferation or apoptosis. This marked contrast between the two species may reflect the different origins of the yolk sac hemangiogenic lineages in mouse and human. TGFbeta effects on the hypoblast, from which these cell lineages are derived in human, would decrease subsequent differentiation of hematopoietic, endothelial and endodermal cells. By contrast, TGFbeta action on murine hypoblast, while affecting endoderm would not affect the hemangiogenic lineages that are epiblast-derived in the mouse. This study highlights important differences between early human and mouse embryonic development and suggests a role of TGFbeta in human hypoblast differentiation.
Highlights
Current understanding of early human embryonic development is based largely on comparison with the mouse, an organism used extensively for studies on the molecular regulation of early mammalian development because of the ease with which genetic manipulation can be undertaken
To examine the role of TGF in early human vascular development we used the model of differentiating human embryonic stem cell-derived embryoid bodies to recapitulate early stages of embryonic development
TGF was applied for different time frames after initiation of embryoid body cultures to assess its effect on differentiation
Summary
Current understanding of early human embryonic development is based largely on comparison with the mouse, an organism used extensively for studies on the molecular regulation of early mammalian development because of the ease with which genetic manipulation can be undertaken. For instance, have two phases of extraembryonic endoderm formation and limited reliance on the yolk sac circulation. The mouse has one phase of extra-embryonic endoderm generation and utilizes the yolk sac until birth (Pera and Trounson, 2004). EB formation from mouse ES cells has already been extensively utilized and validated as an in vitro model of early mouse development (Feraud et al, 2003; Gendron et al, 1996; Goumans et al, 1999; Hirashima et al, 1999; Ng et al, 2004)
Sign-in/Register to view highlights & summary 
Submitted Version (
Free)
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call