title: A gonogenic stimulated transition of mouse embryonic stem cells with enhanced control of diverse differentiation pathways.
abstract: Embryonic stem (ES) cells share markers with undifferentiated primordial germ cells (PGCs). Here, we discovered that a cellular state with some molecular markers of male gonocyte induction, including a G1/S phase arrest and upregulation of specific genes such as Nanos2, Tdrd1, Ddx4, Zbtb16 and Plk1s1, can be chemically induced in male mouse ES cells in vitro, which we termed gonogenic stimulated transition (GoST). After longer culture of the resulting GoST cells without chemical stimulation, several molecular markers typical for early gonocytes were detected including the early gonocyte marker Tex101. Motivated by previous studies that found multipotency in cell lines derived from neonatal male germ cells in vitro, we then compared the differentiation potential of GoST cells to that of ES cells in vitro. Interestingly, GoST cells showed equal neurogenic, but enhanced cardiogenic and hepatogenic differentiation compared to ES cells in vitro. This work shows for the first time that some important molecular markers of the first developmental sexual differentiation program can be induced in male mouse ES cells in vitro and defines a novel concept to generate cells with enhanced multipotency.
authors.affiliation: ETH Zurich, Department of Health Sciences and Technology, Laboratory of Applied Mechanobiology Vladimir Prelog-Weg 4, CH-8093 Zurich, Switzerland.
authors.forename: Cameron
authors.initials: C
authors.lastname: Moshfegh
authors.affiliation: ETH Zurich, Department of Health Sciences and Technology, Laboratory of Applied Mechanobiology Vladimir Prelog-Weg 4, CH-8093 Zurich, Switzerland.
authors.forename: Lina
authors.initials: L
authors.lastname: Aires
authors.affiliation: ETH Zurich, Flow Cytometry Core Facility, Otto-Stern-Weg 7, CH-8093 Zurich, Switzerland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kisielow
authors.affiliation: ETH Zurich, Department of Health Sciences and Technology, Laboratory of Applied Mechanobiology Vladimir Prelog-Weg 4, CH-8093 Zurich, Switzerland.
authors.forename: Viola
authors.initials: V
authors.lastname: Vogel
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice