Abstract
Abnormal placentation is considered as an underlying cause of various pregnancy complications such as miscarriage, preeclampsia and intrauterine growth restriction, the latter increasing the risk for the development of severe disorders in later life such as cardiovascular disease and type 2 diabetes. Despite their importance, the molecular mechanisms governing human placental formation and trophoblast cell lineage specification and differentiation have been poorly unravelled, mostly due to the lack of appropriate cellular model systems. However, over the past few years major progress has been made by establishing self-renewing human trophoblast stem cells and 3-dimensional organoids from human blastocysts and early placental tissues opening the path for detailed molecular investigations. Herein, we summarize the present knowledge about human placental development, its stem cells, progenitors and differentiated cell types in the trophoblast epithelium and the villous core. Anatomy of the early placenta, current model systems, and critical key regulatory factors and signalling cascades governing placentation will be elucidated. In this context, we will discuss the role of the developmental pathways Wingless and Notch, controlling trophoblast stemness/differentiation and formation of invasive trophoblast progenitors, respectively.
Highlights
Formation of the placenta, the unique exchange organ between mother and fetus, is essential for successful human pregnancy and fetal health
Human TEAD4 localizes to the nuclei of proliferative cytotropho blasts (CTBs) of 2D-tropho blast stem cell (TSC) and trophoblast organoids (TB-ORGs), and of placental villous cyto trophoblasts (vCTB) in vivo, while its expression is downreg ulated in cell columns of anchoring villi [33, 34, 113, 186]
caudal-related homeobox transcription fac tor 2 (CDX2) is largely absent from vCTBs of distal villi of early placentae and its expression could not be maintained in self-renewing TB-ORGs at higher pas sage numbers [34, 186]
Summary
The unique exchange organ between mother and fetus, is essential for successful human pregnancy and fetal health. STB, generated by treatment of human embryonic stem cells (hESC) with bone morphogenetic protein 4 (BMP4), could be representative of the early PS, since gene expression in that model is different to that of term STB [96].
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