title: A Resource for the Transcriptional Signature of Bona Fide Trophoblast Stem Cells and Analysis of Their Embryonic Persistence.
abstract: Trophoblast stem cells (TSCs) represent the multipotent progenitors that give rise to the different cells of the embryonic portion of the placenta. Here, we analysed the expression of key TSC transcription factors Cdx2, Eomes, and Elf5 in the early developing placenta of mouse embryos and in cultured TSCs and reveal surprising heterogeneity in protein levels. We analysed persistence of TSCs in the early placenta and find that TSCs remain in the chorionic hinge until E9.5 and are lost shortly afterwards. To define the transcriptional signature of bona fide TSCs, we used inducible gain- and loss-of-function alleles of Eomes or Cdx2, and Eomes (GFP), to manipulate and monitor the core maintenance factors of TSCs, followed by genome-wide expression profiling. Combinatorial analysis of resulting expression profiles allowed for defining novel TSC marker genes that might functionally contribute to the maintenance of the TSC state. Analyses by qRT-PCR and in situ hybridisation validated novel TSC- and chorion-specific marker genes, such as Bok/Mtd, Cldn26, Duox2, Duoxa2, Nr0b1, and Sox21. Thus, these expression data provide a valuable resource for the transcriptional signature of bona fide and early differentiating TSCs and may contribute to an increased understanding of the transcriptional circuitries that maintain and/or establish stemness of TSCs.
authors.affiliation: Renal Department, Centre for Clinical Research, University Medical Centre, Breisacher Strasse 66, 79106 Freiburg, Germany.
authors.forename: Georg
authors.identifier: 0000-0002-5424-2860
authors.initials: G
authors.lastname: Kuales
authors.affiliation: Renal Department, Centre for Clinical Research, University Medical Centre, Breisacher Strasse 66, 79106 Freiburg, Germany.
authors.forename: Matthias
authors.identifier: 0000-0002-0438-4625
authors.initials: M
authors.lastname: Weiss
authors.affiliation: Renal Department, Centre for Clinical Research, University Medical Centre, Breisacher Strasse 66, 79106 Freiburg, Germany.
authors.forename: Oliver
authors.identifier: 0000-0003-4571-5168
authors.initials: O
authors.lastname: Sedelmeier
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Centre, Freiburg, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Pfeifer
authors.affiliation: Renal Department, Centre for Clinical Research, University Medical Centre, Breisacher Strasse 66, 79106 Freiburg, Germany; Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, Freiburg, Germany; BIOSS, Centre for Biological Signalling Studies, Albert Ludwigs University, Freiburg, Germany.
authors.forename: Sebastian J
authors.initials: SJ
authors.lastname: Arnold