Purpose: Human trophoblast stem cells (hTSCs) are counterparts of the precursor cells of the placenta and are valuable cell models for the study of placental development and the pathogenesis of placental diseases. The aim of this work was to establish a triploid human TSC (hTSC) derived from the tripronuclear embryos, which are clinically discarded but readily available, for potential applications in basic placental research and disease modeling.
Methods: Eighteen tripronuclear human zygotes from IVF were collected and cultured for 5-6 days. Five high-quality blastocysts were harvested and were individually cultured in hTSC medium. Finally, two hTSC lines were established after 10 days and could be passaged stably.
Results: The karyotyping analysis showed that hTSC contained three sets of chromosomes. And the hTSC exhibited typical features of hTSCs, with the ability to differentiate into two trophoblast lineages: extravillous cytotrophoblasts (EVTs) and syncytiotrophoblasts (STs). In addition, the hTSC can mimic some vital features of trophoblast, including hormone secretion and invasion. Further studies showed that the proliferation and differentiation of hTSC were reduced compared with normal hTSCs, which may be related to the disturbed metabolic signaling in hTSC.
Conclusions: We established the triploid hTSC lines derived from tripronuclear embryos, which provides a potentially useful research model in vitro to study human placental biology and diseases.
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http://dx.doi.org/10.1007/s10815-022-02436-w | DOI Listing |
Unlabelled: Zika virus (ZIKV) infection can lead to a variety of clinical outcomes, including severe congenital abnormalities. The phosphatidylserine (PS) receptors AXL and TIM-1 are recognized as critical entry factors for ZIKV . However, it remains unclear if and how ZIKV regulates these receptors during infection.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Reproductive Biology Laboratory, Amsterdam University Medical Center Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Placentation disorders, including severe preeclampsia and fetal growth restriction, have their origins in early pregnancy, whereas symptoms typically present later on. To investigate the pathogenesis of these diseases, there is a need for a reliable in vitro model system of early placenta development with known pregnancy outcomes. Therefore, we optimized the generation of human induced trophoblast stem cells (iTSCs) from term umbilical cord, enabling non-invasive collection of patient-derived material immediately after birth.
View Article and Find Full Text PDFCell Stem Cell
December 2024
Loke Centre for Trophoblast Research, University of Cambridge, Cambridge, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK. Electronic address:
The placental DNA methylation landscape is unique, with widespread partially methylated domains (PMDs). The placental "methylome" is conserved across mammals, a shared feature of many cancers, and extensively studied for links with pregnancy complications. Human trophoblast stem cells (hTSCs) offer exciting potential for functional studies to better understand this epigenetic feature; however, whether the hTSC epigenome recapitulates primary trophoblast remains unclear.
View Article and Find Full Text PDFCells Dev
January 2025
Department of Biomedical Engineering, University of Connecticut, Storrs, CT, United States of America; Department of Biomedical Engineering, University of Connecticut Health, Farmington, CT, United States of America; Jackson Laboratory, Farmington, CT, United States of America. Electronic address:
The maternal-fetal interface has long been considered as a frontier for an evolutionary arms race due to the close juxtaposition of genetically distinct tissues. In hemochorial species with deep placental invasion, including in humans, maternal stroma prepares its defenses against deep trophoblast invasion by decidualization, a differentiation process characterized by increased stromal cell matrix production, and contractile force generation. Decidualization has evolved from an ancestral wound healing response of fibroblast activation by the endometrial stroma.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Obstetrics and Gynaecology, University of Cambridge, NIHR Cambridge Biomedical Research Centre, Cambridge, United Kingdom.
The placenta is the critical interface between mother and fetus, and consequently, placental dysfunction underlies many pregnancy complications. Placental formation requires an adequate expansion of trophoblast stem and progenitor cells followed by finely tuned lineage specification events. Here, using single-cell RNA sequencing of mouse trophoblast stem cells during the earliest phases of differentiation, we identify gatekeepers of the stem cell state, notably Nicol1, and uncover unsuspected trajectories of cell lineage diversification as well as regulators of lineage entry points.
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