To date we lack defined protocols that would result in directed, homogenous differentiation of TS cells into specific placental cell types. We use combinations of growth factors and pharmacological inhibitors during TS cell differentiation to decipher the pathways determining cell fate decisions that lead to distinct trophoblast lineages.
The Mek/Erk branch of the Fgf signalling pathway is essential to drive TS cell self-renewal. It is transduced via reversible protein phosphorylation but the mechanism of how phosphorylated Erk drives TS cell identity remains unknown. In order to identify critical factors downstream of Fgf/Erk signalling in TS cells, we employ mass spectrometry for phosphopeptide identification and we have identified a number of candidate targets of Erk that await functional validation.
Mammalian placentas are composite organs consisting of trophoblast descendants and mesodermal derivatives giving rise to umbilical cord and the fetal portion of placental vasculature. These two components come together during embryonic development in a process called chorio-allantoic fusion. Our goal is to model this process in placental organoids.