Trophoblast stem cell derivation from naive and primed hPSC enables ELF5 functional analysis.

IF 5.1 2区医学 Q1 CELL & TISSUE ENGINEERING

Stem Cell Reports Pub Date : 2025-09-03 DOI:10.1016/j.stemcr.2025.102637

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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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.

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从原始和引物的hPSC衍生的滋养细胞干细胞使ELF5功能分析成为可能。

人多能干细胞（hPSCs）是研究胎盘生物学的重要工具，但其分化为真正的滋养细胞干细胞（TSCs）仍然具有挑战性。在这项研究中，我们建立并彻底比较了原始的和引物衍生的tsc样细胞与来自着床前囊胚和妊娠早期胎盘的原代人tsc。综合分析证实了滋养细胞谱系特异性基因的表达和典型的胎盘特征。详细的转录分析表明，天然来源的TSC样细胞与胚胎和胎盘来源的细胞系相似，并且比引物来源的细胞更快、更直接地分化为TSC。我们使用这些TSC样模型来研究ELF5的作用，ELF5是小鼠TSC维持和分化不可或缺的转录因子。与小鼠相比，敲除和敲低实验表明，ELF5对于人类tsc样细胞的自我更新和分化是必不可少的。我们的研究提供了有价值的转录数据，并强调了hpsc衍生的tsc样细胞在建模胎盘和研究基因功能方面的实用性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY

CiteScore

10.50

自引率

1.70%

发文量

200

审稿时长

28 weeks

期刊介绍： 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.