title: Derivation of Pluripotent Cells from Mouse SSCs Seems to Be Age Dependent.
abstract: Here, we aimed to answer important and fundamental questions in germ cell biology with special focus on the age of the male donor cells and the possibility to generate embryonic stem cell- (ESC-) like cells. While it is believed that spermatogonial stem cells (SSCs) and truly pluripotent ESC-like cells can be isolated from adult mice, it remained unknown if the spontaneous conversion of SSCs to ESC-like cells fails at some age. Similarly, there have been differences in the literature about the duration of cultures during which ESC-like cells may appear. We demonstrate the possibility to derive ESC-like cells from SSC cultures until they reach adolescence or up to 7 weeks of age, but we point out the impossibility to derive these cells from older, mature adult mice. The inability of real adult SSCs to shift to a pluripotent state coincides with a decline in expression of the core pluripotency genes Oct4, Nanog, and Sox2 in SSCs with age. At the same time genes of the spermatogonial differentiation pathway increase. The generated ESC-like cells were similar to ESCs and express pluripotency markers. In vitro they differentiate into all three germ lineages; they form complex teratomas after transplantation in SCID mice and produce chimeric mice.
authors.affiliation: Institute for Anatomy and Cell Biology, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany ; Department of Stem Cells and Developmental Biology at the Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, P.O. Box 19395, Tehran 4644, Iran ; Faculty of Veterinary Medicine, Amol University of Special Modern Technologies, P.O. Box 49767, Amol 49767, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Azizi
authors.affiliation: P.O. Box 12 43, 72072 Tübingen, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Conrad
authors.affiliation: Institute for Anatomy and Cell Biology, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Hinz
authors.affiliation: Department of Stem Cells and Developmental Biology at the Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, P.O. Box 19395, Tehran 4644, Iran.
authors.forename: Behrouz
authors.initials: B
authors.lastname: Asgari
authors.affiliation: Institute for Anatomy and Cell Biology, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Nanus
authors.affiliation: Division of Signal Transduction and Growth Control, DKFZ/ZMBH Alliance, Heidelberg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Peterziel
authors.affiliation: Department of Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran.
authors.forename: Akbar
authors.initials: A
authors.lastname: Hajizadeh Moghaddam
authors.affiliation: Department of Stem Cells and Developmental Biology at the Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, P.O. Box 19395, Tehran 4644, Iran ; Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Baharvand
authors.affiliation: Institute for Anatomy and Cell Biology, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Skutella