title: Lineage conversion of murine extraembryonic trophoblast stem cells to pluripotent stem cells.
abstract: In mammals, the first cell fate decision is initialized by cell polarization at the 8- to 16-cell stage of the preimplantation embryo. At this stage, outside cells adopt a trophectoderm (TE) fate, whereas the inside cell population gives rise to the inner cell mass (ICM). Prior to implantation, transcriptional interaction networks and epigenetic modifications divide the extraembryonic and embryonic fate irrevocably. Here, we report that extraembryonic trophoblast stem cell (TSC) lines are converted to induced pluripotent stem cells (TSC-iPSCs) by overexpressing Oct4, Sox2, Klf4, and cMyc. Methylation studies and gene array analyses indicated that TSC-iPSCs had adopted a pluripotent potential. The rate of conversion was lower than those of somatic reprogramming experiments, probably due to the unique genetic network controlling extraembryonic lineage fixation. Both in vitro and in vivo, TSC-iPSCs differentiated into tissues representing all three embryonic germ layers, indicating that somatic cell fate could be induced. Finally, TSC-iPSCs chimerized the embryo proper and contributed to the germ line of mice, indicating that these cells had acquired full somatic differentiation potential. These results lead to a better understanding of the molecular processes that govern the first lineage decision in mammals.
authors.affiliation: Department of Developmental Pathology, Institute of Pathology, University of Bonn Medical School, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kuckenberg
authors.forename: Michael
authors.initials: M
authors.lastname: Peitz
authors.forename: Caroline
authors.initials: C
authors.lastname: Kubaczka
authors.forename: Astrid
authors.initials: A
authors.lastname: Becker
authors.forename: Angela
authors.initials: A
authors.lastname: Egert
authors.forename: Eva
authors.initials: E
authors.lastname: Wardelmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
authors.forename: Oliver
authors.initials: O
authors.lastname: Brüstle
authors.forename: Hubert
authors.initials: H
authors.lastname: Schorle
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D044127:Epigenesis, Genetic; D000090062:Kruppel-Like Factor 4; D051379:Mice; D008810:Mice, Inbred C57BL; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism