Barroca Vilma, Lassalle Bruno, Coureuil Mathieu, Louis Jean Paul, Le Page Florence, Testart Jacques, Allemand Isabelle, Riou Lydia, Fouchet Pierre
Laboratoire Gamétogenèse, Apoptose et Génotoxicité, INSERM U566, Institut de Radiobiologie Cellulaire et Moléculaire, Direction des Sciences du Vivant, CEA, 92265 Fontenay aux Roses, France.
Nat Cell Biol. 2009 Feb;11(2):190-6. doi: 10.1038/ncb1826. Epub 2008 Dec 21.
In adults, stem cells are responsible for the maintenance of many actively renewing tissues, such as haematopoietic, skin, gut and germinal tissues. These stem cells can self-renew or be committed to becoming progenitors. Stem-cell commitment is thought to be irreversible but in male and female Drosophila melanogaster, it was shown recently that differentiating germ cells can revert to functional stem cells that can restore germinal lineage. Whether progenitors are also able to generate stem cells in mammals remains unknown. Here we show that purified mouse spermatogonial progenitors committed to differentiation can generate functional germinal stem cells that can repopulate germ-cell-depleted testes when transplanted into adult mice. We found that GDNF, a key regulator of the stem-cell niche, and FGF2 are able to reprogram in vitro spermatogonial progenitors for reverse differentiation. This study supports the emerging concept that the stem-cell identity is not restricted in adults to a definite pool of cells that self-renew, but that stemness could be acquired by differentiating progenitors after tissue injury and throughout life.
在成体中，干细胞负责维持许多持续活跃更新的组织，如造血组织、皮肤、肠道和生殖组织。这些干细胞能够自我更新，或者分化为祖细胞。干细胞的分化通常被认为是不可逆的，但是最近在雄性和雌性黑腹果蝇中发现，正在分化的生殖细胞可以逆转为功能性干细胞，从而恢复生殖系。在哺乳动物中，祖细胞是否也能够产生干细胞仍然未知。在此，我们表明，纯化的已决定分化的小鼠精原祖细胞能够产生功能性生殖干细胞，将其移植到成年小鼠体内时，这些干细胞能够重新填充生殖细胞耗竭的睾丸。我们发现，干细胞微环境的关键调节因子GDNF和FGF2能够在体外对精原祖细胞进行重编程，使其逆向分化。这项研究支持了一个新出现的概念，即成体中的干细胞身份并不局限于特定的自我更新细胞池，而是在组织损伤后以及整个生命过程中，分化的祖细胞也能够获得干性。
