From yeasts to mammals, the molecular machinery and chromosome structures carrying out meiosis are frequently conserved. However, the signal to initiate meiosis appears divergent: while nutrient restriction induces meiosis in the yeast system, retinoic acid (RA), a chordate morphogen, is necessary but not sufficient to induce meiotic initiation in mammalian germ cells via its target, Stra8. Here, using cultured mouse male germline stem cells without the support of gonadal somatic cells, we show that nutrient restriction in combination with RA robustly induces Spo11-dependent meiotic DNA double strand breaks (DSBs) and Stra8-dependent meiotic gene programs recapitulating those of early meiosis in vivo. Moreover, a distinct network of 11 nutrient restriction-upregulated transcription factor genes was identified, whose expression does not require RA and is associated with early meiosis in vivo. Thus, our study proposes a conserved model, in which nutrient restriction induces meiotic initiation by upregulating transcriptional factors for meiotic gene programs, and provides an in vitro platform to derive haploid gametes in culture.

中文翻译：

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营养限制，酵母减数分裂的诱导剂，诱导哺乳动物减数分裂的起始

从酵母到哺乳动物，进行减数分裂的分子机制和染色体结构经常得到保护。但是，引发减数分裂的信号似乎存在分歧：虽然营养限制会导致酵母系统减数分裂，但一种维甲酸（Chordate morphogen）的视黄酸（RA）是必需的，但不足以通过其靶标Stra8诱导哺乳动物生殖细胞的减数分裂启动。在这里，使用没有性腺体细胞支持的培养的小鼠雄性种系干细胞，我们显示营养限制与RA结合可强烈诱导Spo11依赖的减数分裂DNA双链断裂（DSB）和Stra8依赖的减数分裂基因程序，概括了早期的那些体内减数分裂。此外，鉴定了一个独特的网络，其中包含11种营养素限制性上调的转录因子基因，其表达不需要RA，并且与体内早期减数分裂有关。因此，我们的研究提出了一个保守的模型，其中营养限制通过上调减数分裂基因程序的转录因子来诱导减数分裂起始，并提供了一个体外平台来衍生培养物中的单倍体配子。