title: Mouse differentiating spermatogonia can generate germinal stem cells in vivo.
abstract: 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.
authors.affiliation: Laboratoire Gamétogenèse, Apoptose et Génotoxicité, INSERM U566, Institut de Radiobiologie Cellulaire et Moléculaire, Direction des Sciences du Vivant, CEA, 92265 Fontenay aux Roses, France.
authors.forename: Vilma
authors.initials: V
authors.lastname: Barroca
authors.forename: Bruno
authors.initials: B
authors.lastname: Lassalle
authors.forename: Mathieu
authors.initials: M
authors.lastname: Coureuil
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Louis
authors.forename: Florence
authors.initials: F
authors.lastname: Le Page
authors.forename: Jacques
authors.initials: J
authors.lastname: Testart
authors.forename: Isabelle
authors.initials: I
authors.lastname: Allemand
authors.forename: Lydia
authors.initials: L
authors.lastname: Riou
authors.forename: Pierre
authors.initials: P
authors.lastname: Fouchet
mesh_terms: D000818:Animals; D054337:Cell Dedifferentiation / Q000187:drug effects / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics*; D049109:Cell Proliferation; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012038:Regeneration / Q000187:drug effects / Q000502:physiology; D013093:Spermatogonia / Q000166:cytology / Q000378:metabolism*; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013737:Testis / Q000166:cytology / Q000378:metabolism
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; C485184:enhanced green fluorescent protein; D016222:Fibroblast Growth Factor 2; D049452:Green Fluorescent Proteins