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Trophoblast stem cell derivation from naive and primed hPSC enables ELF5 functional analysis (scRNAseq)

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281595 | GEO | 2025/09/15

REPOSITORIES: GEO

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Trophoblast stem cell derivation from naive and primed hPSC enables ELF5 functional analysis (miRNAseq)

Project description: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.

2025-09-15 | GSE297156 | GEO

Elf5-centered transcription factor hub controls trophoblast stem cell self-renewal and differentiation through stoichiometry-sensitive shifts in target gene networks

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Transcriptome profiling of human cytomegalovirus-infected trophoblasts

Project description:Placental infection plays a central role in the pathogenesis of congenital human cytomegalovirus (HCMV) infections and is a cause of fetal growth restriction and pregnancy loss. HCMV can replicate in some trophoblast cell types, but it remains unclear how the virus evades antiviral immunity in the placenta and how infection compromises placental development and function. Human trophoblast stem cells (TSCs) can be differentiated into extravillous trophoblasts (EVTs) and syncytiotrophoblasts (STBs). This study assessed the utility of TSCs as a model of HCMV infection in the first trimester placenta. TSCs and TSC-derived EVTs and STBs were infected with HCMV (TB40/Ewt-mCherry). RNA was isolated from infected cells at 24, 48, and 72 hours post-infection and Illumina RNA-Sequencing was used to measure viral and host gene expression. Viral gene expression in TSCs does not follow the kinetic patterns observed during lytic infection in fibroblasts. Canonical antiviral responses were largely not observed in HCMV-infected TSCs and TSC-derived trophoblasts. Rather, infection dysregulated factors involved in cell identity, differentiation, and WNT signaling.

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Human primed and naive PSCs are equally potent in differentiating into bona fide trophoblast stem cells (RNA-Seq)

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