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Introduction
The placenta is a critical organ that allows the fetus to develop within the female reproductive tract1. Specialized functions attributed to the placenta are executed by trophoblast cells2, 3–4. The trophoblast cell lineage arises from the initial differentiation event of the embryo5. In the human, trophoblast cells organize into villous and extravillous structures. A villous is comprised of trophoblast and non-trophoblast cell types and includes a self-renewing trophoblast cell population referred to as cytotrophoblast6,7. Cytotrophoblast are the progenitors for two differentiated cell populations: syncytiotrophoblast (STB) and extravillous trophoblast (EVT) cells2, 3–4. STBs have a fundamental role in regulating nutrient and waste transfer between mother and fetus6, whereas EVT cells exit the placenta and transform the uterus into an environment supporting placental and fetal development2,3. Failures in placentation are the root cause of an assortment of disorders of pregnancy, including early pregnancy loss, preeclampsia, intrauterine growth restriction, and pre-term birth8,9. Regulatory mechanisms underlying human cytotrophoblast self-renewal and differentiation have largely remained elusive.
Recently, conditions for capturing and maintaining human trophoblast stem (TS) cells in vitro were described10. Human TS cells have the capacity for self-renewal and differentiation into STB or EVT cells. This in vitro model system has led to the generation of new insights into mechanisms regulating human trophoblast cell development11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21–22. Initial human TS cell lines were derived from blastocysts or first-trimester placental tissue obtained from pregnancy terminations. Establishment of culture conditions for human TS cells led to the derivation of TS cells from pluripotent stem cells23, 24, 25, 26, 27, 28–29. These in vitro model systems have provided new insights regarding trophoblast cell development; however, it is unknown whether the origin of these TS cells was compatible with a healthy pregnancy outcome.
Chorionic villus sampling (CVS) represents a standard prenatal care procedure that is performed between 10 and 14 weeks of gestation30. Sampling involves the removal of a small amount of chorionic villus tissue for the purpose of genetic testing. Common indications for retrieving chorionic villus tissue include advanced maternal age, history of infertility, family history (e.g., sibling with...