Joonas Sokka, Ella Lapinsuo, Jouni Kvist, Sami Jalil, Masahito Yoshihara, Jere Weltner, Fredrik Lanner, Juha Kere, Diego Balboa, Timo Otonkoski, Ras Trokovic
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Trophoblast stem cell derivation from naive and primed hPSC enables ELF5 functional analysis.
Human pluripotent stem cells (hPSCs) are valuable tools for studying placental biology, yet their differentiation into bona fide trophoblast stem cells (TSCs) remains challenging. In this study, we established and thoroughly compared naive and primed-derived TSC-like cells with primary human TSCs derived from pre-implantation blastocyst and first-trimester placenta. Comprehensive analyses confirmed expression of trophoblast lineage-specific genes and typical placental features. Detailed transcriptional analyses revealed that naive-derived TSC-like cells resembled embryo and placenta-derived cell lines and differentiated faster and more directly into TSC than primed-derived cells. We used these TSC-like models to study the role of ELF5, a transcription factor indispensable for maintenance and differentiation in mouse TSC. In contrast to the mouse, knockout and knockdown experiments revealed that ELF5 is dispensable for human TSC-like cells self-renewal and differentiation. Our study provides valuable transcriptional data and highlights the utility of hPSC-derived TSC-like cells for modeling the placenta and studying gene function.
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Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.
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