Human neural stem cells (hNSCs) have long been used as an in vitro model to study neurogenesis and as candidates for nervous system therapy. Many parameters have been considered when evaluating the success of transplantation, but sex of donor and recipients is often not discussed. We investigated two commercial NSC lines, the female hNSC-H9 and male hNSC-H14, and we observed faster growth rates in the male cells. At 4 days of differentiation, male cells presented a significant increase in expression of DCX, an immature neuronal marker, while female cells showed a significant increase in RMST, a long noncoding RNA, which is indispensable during neurogenesis. In addition, expression of neural markers MAP2, PSD95, SYP, DCX, and TUJ1 at day 14 of differentiation suggested a similar differentiation potential in both lines. The most significant differences at day 14 of differentiation were the expression levels of RELN, with almost 100-fold difference between the sexes, and MASH1, with more than 1,000-fold increase in male cells. To evaluate whether some of the observed differences may be sex related, we measured the expression of gametologous genes located on the X- and Y-chromosome. Most noticeable was the increase of Y-encoded demethylases KDM6C (UTY) and KDM5D during differentiation of male cells. Our results indicate that attention should be paid to sex when planning neurogenesis and transplantation experiments.

中文翻译：

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在人类男性神经干细胞分化过程中增加 Y 编码的去甲基化酶的表达

人类神经干细胞 (hNSCs) 长期以来一直被用作研究神经发生的体外模型和神经系统治疗的候选者。在评估移植成功率时考虑了许多参数，但通常不讨论供者和受者的性别。我们研究了两种商业 NSC 系，雌性 hNSC-H9 和雄性 hNSC-H14，我们观察到雄性细胞的生长速度更快。在分化的第 4 天，雄性细胞表现出DCX（一种未成熟的神经元标记物）表达显着增加，而雌性细胞表现出RMST（一种长链非编码 RNA，在神经发生过程中必不可少）的表达显着增加。此外，神经标志物MAP2、PSD95、SYP的表达、DCX和TUJ1在分化第 14 天表明两种品系具有相似的分化潜能。分化第 14 天最显着的差异是RELN的表达水平，两性之间的差异几乎是 100 倍，而MASH1的表达水平则是雄性细胞增加了 1,000 多倍。为了评估观察到的某些差异是否可能与性别有关，我们测量了位于 X 和 Y 染色体上的配子体基因的表达。最显着的是 Y 编码的去甲基化酶 KDM6C ( UTY ) 和KDM5D 的增加在雄性细胞分化过程中。我们的结果表明，在规划神经发生和移植实验时应注意性。