Abstract
The origin and regulation of stem cells sustaining trophoblast renewal in the human placenta remain unclear. Decorin, a leucine-rich proteoglycan restrains trophoblast proliferation, migration/invasiveness and endovascular differentiation, and local decorin overproduction is associated with preeclampsia (PE). Here, we tested the role of decorin in human trophoblast stem cell self-renewal and differentiation, using two models: an immortalized first trimester trophoblast cell line HTR-8/SVneo (HTR) and freshly isolated primary trophoblast (p-trophoblast) from early first trimester (6–9 weeks) placentas. Self-renewal capacity was measured by spheroid forming ability of single cells on ultra-low attachment plates for multiple generations. Markers of embryonic stem (ES) cells, trophoblast stem (TS) cells and trophoblast were used to identify stem cell hierarchy. Differentiation markers for syncytial and extravillous (EVT) pathways were employed to identify differentiated cells. Bewo cells were additionally used to explore DCN effects on syncytialization. Results reveal that the incidence of spheroid forming stem-like cells was 13–15% in HTR and 0.1–0.4%, in early first trimester p-trophoblast, including a stem cell hierarchy of two populations of ES and TS-like cells. DCN restrained ES cell self-renewal, promoted ES to TS transition and maintenance of TS cell stem-ness, but inhibited TS cell differentiation into both syncytial and EVT pathways.
Highlights
Embryonic trophectoderm, the precursor of trophoblast cells of the placenta is the first epithelium appearing during mammalian development
Until very recently (2018) no good model was available to study the dual properties of human trophoblast stem cells i.e., self-renewal and differentiation at the same time
Okae et al.[10] reported long term culture of first trimester human trophoblast cells in special culture conditions which differentiated to both STB and extravillous trophoblast (EVT) pathways
Summary
The precursor of trophoblast cells of the placenta is the first epithelium appearing during mammalian development. Human embryonic stem cells lines (hESC) have been successfully manipulated in vitro with bone morphogenetic protein (BMP) 4 treatment to obtain cells with STB and EVT phenotype[4,5,6,7].The latter authors[7] showed that hESCs after exposure to BMP4 and two small compounds, an activin A signaling inhibitor and a FGF2 signaling inhibitor (BMP4/A83–01/PD173074; BAP) commit to trophoblast lineages identified by markers of CTB and STB They proposed that the STB generated from the differentiated hESC (hESC-d) represents the primitive invasive syncytium encountered in early pregnancy prior to the development of the chorionic villi. Bewo trophoblast cells were used to examine the role of DCN in syncytial differentiation
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