Human perinatal stem cells (SCs) can be isolated from fetal annexes without ethical or safety limitations. They are generally considered multipotent; nevertheless, their biological characteristics are still not fully understood. The aim of this study was to investigate the pluripotency potential of human perinatal SCs as compared to human induced pluripotent stem cells (hiPSCs). Despite the low expression of the pluripotent factors NANOG, OCT4, SOX2, and C-KIT in perinatal SC, we observed minor differences in the promoters DNA-methylation profile of these genes with respect to hiPSCs; we also demonstrated that in perinatal SCs miR-145-5p had an inverse trend in comparison to these stemness markers, suggesting that NANOG, OCT4, and SOX2 were regulated at the post-transcriptional level. The reduced expression of stemness markers was also associated with shorter telomere lengths and shift of the oxidative metabolism between hiPSCs and fetal annex-derived cells. Our findings indicate the differentiation ability of perinatal SCs might not be restricted to the mesenchymal lineage due to an epigenetic barrier, but other regulatory mechanisms such as telomere shortening or metabolic changes might impair their differentiation potential and challenge their clinical application.

中文翻译：

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人类围产期干细胞的表观遗传特征重新定义了其干势。

可以从胎儿附件中分离出人类围产期干细胞（SCs），而没有道德或安全限制。它们通常被认为是多能的。然而，它们的生物学特性仍然没有被完全理解。这项研究的目的是研究与人类诱导的多能干细胞（hiPSC）相比，人类围产期SC的多能潜能。尽管围产期SC中多能因子NANOG，OCT4，SOX2和C-KIT的表达较低，但我们观察到这些基因相对于hiPSC的启动子DNA甲基化谱存在细微差异。我们还证明，在围产期SC中，与这些干性标记相比，miR-145-5p具有相反的趋势，这表明NANOG，OCT4和SOX2在转录后水平受到调控。茎标记的表达减少还与较短的端粒长度和hiPSC与胎儿附件衍生细胞之间的氧化代谢转变有关。我们的发现表明，由于表观遗传障碍，围产期SC的分化能力可能不限于间充质谱系，但其他调节机制（例如端粒缩短或代谢改变）可能会损害其分化潜能，并挑战其临床应用。