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再生医学的重大发现:雄性生殖系对理解多能性的贡献。

Seminal discoveries in regenerative medicine: contributions of the male germ line to understanding pluripotency.

作者信息

Geijsen Niels, Jones D Leanne

机构信息

Harvard Medical School, Massachusetts General Hospital, Center for Regenerative Medicine and Technology, Boston, MA 02114, USA.

出版信息

Hum Mol Genet. 2008 Apr 15;17(R1):R16-22. doi: 10.1093/hmg/ddn084.

DOI:10.1093/hmg/ddn084
PMID:18632691
Abstract

Germ cells are highly specialized cells that form gametes (sperm and eggs), and they are the only cells within an organism that contribute genes to offspring. Due to the fact that the genetic information contained within germ cells is passed from generation to generation, the germ line is often thought of as immortal. Studies have revealed that germ cells are remarkably similar to pluripotent embryonic stem cells (ESCs). For example, there is a significant overlap in the gene expression profile between ESCs and primordial germ cells (PGCs), the founders of the germ cell lineage. In addition, pluripotent embryonic germ (EG) cell lines have been derived from mammalian PGCs. Secondly, a subset of testicular germ cell tumors, known as non-seminomas, often contain differentiated cells representative of all three germ layers, a definitive test of pluripotency. Lastly, recent results have demonstrated the ability of spermatogonial stem cells (SSCs) to de-differentiate into pluripotent ES-like cells, underscoring a unique relationship between the germ line and pluripotent cells that are present during the earliest stages of embryonic development. Here, we will review the factors that regulate the self-renewal and maintenance of male germline stem cells (GSCs) and discuss how these factors may allow us to manipulate the germ line to create pluripotent cells that could serve as a critical tool in cell replacement therapies and regenerative medicine.

摘要

生殖细胞是形成配子(精子和卵子)的高度特化细胞,它们是生物体中唯一能将基因传递给后代的细胞。由于生殖细胞中包含的遗传信息代代相传,生殖系通常被认为是不朽的。研究表明,生殖细胞与多能胚胎干细胞(ESCs)非常相似。例如,ESCs和原始生殖细胞(PGCs,生殖细胞谱系的奠基者)之间的基因表达谱有显著重叠。此外,多能胚胎生殖(EG)细胞系已从哺乳动物的PGCs中获得。其次,一种被称为非精原细胞瘤的睾丸生殖细胞肿瘤的一个亚群,通常包含代表所有三个胚层的分化细胞,这是对多能性的决定性测试。最后,最近的研究结果表明,精原干细胞(SSCs)能够去分化为多能性的类ES细胞,这突出了生殖系与胚胎发育早期存在的多能细胞之间的独特关系。在这里,我们将回顾调节雄性生殖系干细胞(GSCs)自我更新和维持的因素,并讨论这些因素如何使我们能够操纵生殖系以创建多能细胞,这些细胞可作为细胞替代疗法和再生医学中的关键工具。

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Seminal discoveries in regenerative medicine: contributions of the male germ line to understanding pluripotency.再生医学的重大发现:雄性生殖系对理解多能性的贡献。
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Mol Biotechnol. 2014 Dec;56(12):1100-9. doi: 10.1007/s12033-014-9790-9.
2
Pluripotency of male germline stem cells.精原干细胞的多能性。
Mol Cells. 2011 Aug;32(2):113-21. doi: 10.1007/s10059-011-1024-4. Epub 2011 Mar 24.
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Spermatogonial stem cells, in vivo transdifferentiation and human regenerative medicine.精原干细胞、体内转分化与人类再生医学。
Expert Opin Biol Ther. 2010 Apr;10(4):519-30. doi: 10.1517/14712591003614731.