Biology and Pathology of the Oocyte: In vitro differentiation of germ cells from stem cells
Biology and Pathology of the Oocyte: In vitro differentiation of germ cells from stem cells
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DOI：
10.1017/cbo9781139135030.021
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发表时间：
2013-10
期刊：
影响因子：
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通讯作者：
Fumihiro Sugawa;K. Hübner;H. Schöler
中科院分区：
文献类型：
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作者：
Fumihiro Sugawa;K. Hübner;H. Schöler
生殖细胞是体内唯一可以将遗传信息传递给下一代的细胞类型，体细胞谱系产生索马或身体[1]。生殖细胞从原始生殖细胞（PGCs）发育成成熟配子涉及一系列复杂的生物学过程，这些过程在给定的时间段内发生，并且可以细分为几个步骤：特化、迁移、表观遗传重编程、性别分化和减数分裂，其中最后一个包括卵子发生或精子发生。基因调控网络的复杂程序严格指导着发育事件的精确顺序。一些基因在生殖细胞中特异性表达，而另一些基因在生殖细胞环境的体细胞组分中特异性表达。还有一些在生殖细胞和体细胞中表达。尽管认识到生殖细胞的重要性，但科学界尚未阐明生殖细胞发育各个步骤的分子机制----这些仍然知之甚少，部分原因是缺乏足够的工具和数量的细胞进行结论性研究。胚胎干细胞（ESC）是来源于植入前囊胚内细胞团（ICM）的细胞[2-4]。这些细胞具有无限自我更新的能力，同时保持多能性的特征，多能性被定义为分化成所有三个胚层（外胚层、内胚层和中胚层）和生殖细胞的细胞类型的潜力。小鼠胚胎干细胞（mESCs）和人类胚胎干细胞（hESCs）的建立不仅给科学界带来了极大的兴奋，而且也给临床环境带来了极大的兴奋，对这些细胞的潜在用途提出了很高的期望，以拓宽我们对发育和疾病机制的理解。然而，围绕从“人类胚胎”中获得ESC的争议限制了可以获得的细胞系的数量。2000年代中期的一项突破永远改变了干细胞研究领域，并有可能克服这一限制。发现体细胞能够通过四种转录因子Oct 4、Sox 2、Klf 4和c-Myc的异位共表达而被重编程为所谓的诱导多能干细胞（iPSC）[5，6]，这四种转录因子是已知在ESC中维持多能性的四种因子。这种新技术能够衍生出患者特异性的iPSC，用于疾病建模、药物筛选和疾病致病机制的研究。
Introduction Germ cells are the only cell type in the body that can carry genetic information on to the next generation, and the somatic cell lineages give rise to the soma, or body [1]. The development of germ cells from primordial germ cells (PGCs) into mature gametes involves a series of complex biological processes that occur over a given time period and that can be subdivided into several steps: specification, migration, epigenetic reprogramming, sex differentiation, and meiosis, the last of which includes oogenesis or spermatogenesis. A complex program of genetic regulatory networks rigorously directs the precise sequence of developmental events. Some genes are expressed specifically in germ cells, whereas others are expressed specifically in the somatic component of the germ cell environment. Yet still others are expressed in both germ cells and somatic cells. Despite recognizing the importance of germ cells, the scientific community has not yet elucidated the molecular mechanisms underlying the individual steps of germ cell development – these remain poorly understood, owing in part to the lack of sufficient tools and quantities of cells for conclusive studies. Embryonic stem cells (ESCs) are cells derived from the inner cell mass (ICM) of preimplantation blastocysts [2–4]. These cells have the ability to self-renew indefinitely while maintaining the feature of pluripotency, defined as the potential to differentiate into cell types of all three germ layers (ectoderm, endoderm, and mesoderm) and germ cells. The establishment of mouse ESCs (mESCs) and human ESCs (hESCs) brought great excitement not only to the scientific community, but also to the clinical setting, raising high expectations on the potential use of these cells to broaden our understanding of the mechanisms involved in development and disease. However, the controversy surrounding the derivation of ESCs from “human embryos” has limited the number of cell lines that could be derived. A breakthrough in the mid 2000s forever changed the field of stem cell research and has the potential to overcome this limitation. Somatic cells were discovered to be capable of being reprogrammed into so-called induced pluripotent stem cells (iPSCs) [5, 6] by the ectopic co-expression of the four transcription factors Oct4, Sox2, Klf4, and c-Myc – four factors that are known to sustain pluripotency in ESCs. This new technique enables the derivation of patient-specific iPSCs for disease modeling, drug screening, and investigations into the causative mechanisms underlying disease.