Takahashi Natsumi, Davy Philip M C, Gardner Lauren H, Mathews Juanita, Yamazaki Yuki, Allsopp Richard C
Institute for Biogenesis Research, John A Burns School of Medicine, Honolulu, Hawaii, United States of America.
PLoS One. 2016 May 5;11(5):e0154309. doi: 10.1371/journal.pone.0154309. eCollection 2016.
Pluripotent stem cells of the early embryo, and germ line cells, are essential to ensure uncompromised development to adulthood as well as species propagation, respectively. Recently, the transcription factor hypoxia inducible factor 1 alpha (Hif1α) has been shown to have important roles in embryonic stem cells; in particular, regulation of conversion to glycolytic metabolism and, as we have shown, maintenance of functional levels of telomerase. In the present study, we sought to assess whether Hif1α was also expressed in the primitive cells of the murine embryo. We observed expression of Hif1α in pre-implantation embryos, specifically the 2-cell stage, morula, and blastocyst. Robust Hif1α expression was also observed in male and female primordial germ cells. We subsequently assessed whether Hif1α was expressed in adult male and female germ cells. In the testis, Hif1α was robustly expressed in spermatogonial cells, in both juvenile (6-week old) and adult (3-month old) males. In the ovaries, Hif1α was expressed in mature oocytes from adult females, as assessed both in situ and in individual oocytes flushed from super-ovulated females. Analysis of Hif1α transcript levels indicates a mechanism of regulation during early development that involves stockpiling of Hif1α protein in mature oocytes, presumably to provide protection from hypoxic stress until the gene is re-activated at the blastocyst stage. Together, these observations show that Hif1α is expressed throughout the life-cycle, including both the male and female germ line, and point to an important role for Hif1α in early progenitor cells.
早期胚胎的多能干细胞和生殖系细胞,分别对于确保个体发育至成年以及物种繁衍至关重要。最近,转录因子缺氧诱导因子1α(Hif1α)已被证明在胚胎干细胞中具有重要作用;特别是在向糖酵解代谢的转化调控方面,以及如我们所表明的,在端粒酶功能水平的维持方面。在本研究中,我们试图评估Hif1α是否也在小鼠胚胎的原始细胞中表达。我们观察到Hif1α在植入前胚胎中表达,特别是在2细胞期、桑椹胚和囊胚期。在雄性和雌性原始生殖细胞中也观察到了强烈的Hif1α表达。随后,我们评估了Hif1α是否在成年雄性和雌性生殖细胞中表达。在睾丸中,Hif1α在幼年(6周龄)和成年(3月龄)雄性的精原细胞中均有强烈表达。在卵巢中,通过原位分析以及从超排卵雌性中冲洗出的单个卵母细胞分析评估,Hif1α在成年雌性的成熟卵母细胞中表达。对Hif1α转录水平的分析表明,在早期发育过程中存在一种调控机制,即成熟卵母细胞中储存Hif1α蛋白,推测是为了在基因在囊胚期重新激活之前提供对缺氧应激的保护。总之,这些观察结果表明Hif1α在整个生命周期中都有表达,包括雄性和雌性生殖系,并指出Hif1α在早期祖细胞中具有重要作用。