Moshfegh Cameron, Aires Lina, Kisielow Malgorzata, Vogel Viola
ETH Zurich, Department of Health Sciences and Technology, Laboratory of Applied Mechanobiology Vladimir Prelog-Weg 4, CH-8093 Zurich, Switzerland.
ETH Zurich, Flow Cytometry Core Facility, Otto-Stern-Weg 7, CH-8093 Zurich, Switzerland.
Sci Rep. 2016 May 9;6:25104. doi: 10.1038/srep25104.
Embryonic stem (ES) cells share markers with undifferentiated primordial germ cells (PGCs). Here, we discovered that a cellular state with some molecular markers of male gonocyte induction, including a G1/S phase arrest and upregulation of specific genes such as Nanos2, Tdrd1, Ddx4, Zbtb16 and Plk1s1, can be chemically induced in male mouse ES cells in vitro, which we termed gonogenic stimulated transition (GoST). After longer culture of the resulting GoST cells without chemical stimulation, several molecular markers typical for early gonocytes were detected including the early gonocyte marker Tex101. Motivated by previous studies that found multipotency in cell lines derived from neonatal male germ cells in vitro, we then compared the differentiation potential of GoST cells to that of ES cells in vitro. Interestingly, GoST cells showed equal neurogenic, but enhanced cardiogenic and hepatogenic differentiation compared to ES cells in vitro. This work shows for the first time that some important molecular markers of the first developmental sexual differentiation program can be induced in male mouse ES cells in vitro and defines a novel concept to generate cells with enhanced multipotency.
胚胎干细胞（ES细胞）与未分化的原始生殖细胞（PGC）具有共同的标志物。在此，我们发现一种具有雄性生殖母细胞诱导的某些分子标志物的细胞状态，包括G1/S期停滞以及特定基因（如Nanos2、Tdrd1、Ddx4、Zbtb16和Plk1s1）的上调，可在体外雄性小鼠ES细胞中通过化学诱导产生，我们将其称为生殖原性刺激转变（GoST）。在不进行化学刺激的情况下对所得的GoST细胞进行更长时间的培养后，检测到了几种早期生殖母细胞典型的分子标志物，包括早期生殖母细胞标志物Tex101。受先前研究发现体外源自新生雄性生殖细胞的细胞系具有多能性的启发，我们随后在体外比较了GoST细胞与ES细胞的分化潜能。有趣的是，与体外ES细胞相比，GoST细胞显示出同等的神经源性分化能力，但具有更强的心脏源性和肝脏源性分化能力。这项工作首次表明，首次发育性分化程序的一些重要分子标志物可在体外雄性小鼠ES细胞中诱导产生，并定义了一种产生具有增强多能性细胞的新概念。
