「自然」期刊19日发表研究报告说，男性睾丸日后可能成为便利而又充裕的成人干细胞来源。

　　纽约康乃尔医学院研究人员已从老鼠的睾丸分离出干细胞，并成功的促使它们分化成心脏细胞、脑部细胞，以及能够发挥功能的血管组织。

　　研究报告说，如果这种技术能够适用于人类，将可以避免使用胚胎干细胞引起的道德争议。

　　霍华休斯医学研究所的芮费(Shahin Rafii)领导的实验小组，没有利用基因操控，就成功的培育出多能成体精原干细胞。

　　芮费说，这项研究真正的创举是，这些老鼠干细胞未经任何基因操控，就形成多能细胞，继而发展成各种不同的细胞。这项实验使用的精原祖／干细胞(SPC)，是专门制造精子的先驱细胞。研究报告主要执笔人辛德尔(Marco Seandel)说，SPC效能强大，让男性一直到老年还有生育能力。

　　辛德尔在实验室中发现大量培育SPC的方法，另一个研究小组则负责调配最适当的生化培养液，以促使这些SPC放弃制造生殖细胞的正常功能，接受制造多能干细胞的新任务。

Nature 449, 346-350 (20 September 2007) | doi:10.1038/nature06129; Received 1 June 2007; Accepted 27 July 2007

Generation of functional multipotent adult stem cells from GPR125⁺ germline progenitors

Marco Seandel^1,3, Daylon James¹, Sergey V. Shmelkov¹, Ilaria Falciatori¹, Jiyeon Kim¹, Sai Chavala¹, Douglas S. Scherr², Fan Zhang¹, Richard Torres⁵, Nicholas W. Gale⁵, George D. Yancopoulos⁵, Andrew Murphy⁵, David M. Valenzuela⁵, Robin M. Hobbs^4,6, Pier Paolo Pandolfi^4,6 & Shahin Rafii¹

1.                               Howard Hughes Medical Institute, Department of Genetic Medicine, and,

2.                               Department of Urology, Weill Cornell Medical College, New York 10065, USA

3.                               Division of Medical Oncology, Department of Medicine, and,

4.                               Cancer Biology and Genetics Program, Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York 10065, USA

5.                               Regeneron Pharmaceuticals, Tarrytown, New York 10591, USA

6.                               Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts 02115, USA

Correspondence to: Shahin Rafii¹ Correspondence and requests for materials should be addressed to S.R. (Email: srafii@med.cornell.edu).

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Adult mammalian testis is a source of pluripotent stem cells¹. However, the lack of specific surface markers has hampered identification and tracking of the unrecognized subset of germ cells that gives rise to multipotent cells². Although embryonic-like cells can be derived from adult testis cultures after only several weeks in vitro¹, it is not known whether adult self-renewing spermatogonia in long-term culture can generate such stem cells as well. Here, we show that highly proliferative adult spermatogonial progenitor cells (SPCs) can be efficiently obtained by cultivation on mitotically inactivated testicular feeders containing CD34⁺ stromal cells. SPCs exhibit testicular repopulating activity in vivo and maintain the ability in long-term culture to give rise to multipotent adult spermatogonial-derived stem cells (MASCs). Furthermore, both SPCs and MASCs express GPR125, an orphan adhesion-type G-protein-coupled receptor. In knock-in mice bearing a GPR125– -galactosidase (LacZ) fusion protein under control of the native Gpr125 promoter (GPR125–LacZ), expression in the testis was detected exclusively in spermatogonia and not in differentiated germ cells. Primary GPR125–LacZ SPC lines retained GPR125 expression, underwent clonal expansion, maintained the phenotype of germline stem cells, and reconstituted spermatogenesis in busulphan-treated mice. Long-term cultures of GPR125⁺ SPCs (GSPCs) also converted into GPR125⁺ MASC colonies. GPR125⁺ MASCs generated derivatives of the three germ layers and contributed to chimaeric embryos, with concomitant downregulation of GPR125 during differentiation into GPR125^- cells. MASCs also differentiated into contractile cardiac tissue in vitro and formed functional blood vessels in vivo. Molecular bookmarking by GPR125 in the adult mouse and, ultimately, in the human testis could enrich for a population of SPCs for derivation of GPR125⁺ MASCs, which may be employed for genetic manipulation, tissue regeneration and revascularization of ischaemic organs.