Embryonic stem cells as models of trophoblast differentiation: progress, opportunities, and limitations

Abstract

While the determination of the trophoblast lineage and the facilitation of placental morphogenesis by trophoblast interactions with other cells of the placenta are crucial components for the establishment of pregnancy, these processes are not tractable at the time of human implantation. Embryonic stem cells (ESCs) provide an embryonic surrogate to derive insights into these processes. In this review, we will summarize current paradigms which promote trophoblast differentiation from ESCs, and potential opportunities for their use to further define signals directing morphogenesis of the placenta following implantation of the embryo into the endometrium.

Paracrine and Epigenetic Control of Trophectoderm Differentiation from Human Embryonic Stem Cells: The Role of Bone Morphogenic Protein 4 and Histone Deacetylases

“…Uncertainties in human TE differentiation will remain without a defined in vitro culture that produces TE with high selectivity and efficiency [70]. Protocols using either nonadherent embryoid bodies or adherent hESCs on MEFs produce TE and secrete placental hormones but are heterogeneous [71,72], and thus are not TE selective.…”

Dynamic Changes in Gene Expression during Early Trophoblast Differentiation from Human Embryonic Stem Cells Treated with BMP4

“…The model also affords a means to investigate both extrinsic factors, such as O 2 and various hormones and growth factors, and intrinsic genetic and epigenetic mechanisms that control the emergence and differentiation of TR. Therefore, the BMP4/hESC model system may prove useful for investigating the etiology of pregnancy disorders, such as preeclampsia (Golos, Giakoumopoulos et al 2010;Das, Ezashi et al 2007;Schulz, Ezashi et al 2008). …”

Coordinated Proliferation and Differentiation of Human-Induced Pluripotent Stem Cell-Derived Cardiac Progenitor Cells Depend on Bone Morphogenetic Protein Signaling Regulation by GREMLIN 2

“…H uman embryonic stem (ES) and induced pluripotent stem (iPS) cells differentiate to a variety of distinct tissuespecific cell types, providing a unique resource to study human embryonic development and disease mechanisms [1][2][3][4]. A major challenge in this endeavor is to enrich the differentiation of pluripotent stem cell to specific cell types with desired characteristics [5][6][7][8].…”