title: Cdx2 efficiently induces trophoblast stem-like cells in naïve, but not primed, pluripotent stem cells.
abstract: Diverse pluripotent stem cell lines have been derived from the mouse, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), embryonal carcinoma cells (ECCs), and epiblast stem cells (EpiSCs). While all are pluripotent, these cell lines differ in terms of developmental origins, morphology, gene expression, and signaling, indicating that multiple pluripotent states exist. Whether and how the pluripotent state influences the cell line's developmental potential or the competence to respond to differentiation cues could help optimize directed differentiation protocols. To determine whether pluripotent stem cell lines differ in developmental potential, we compared the capacity of mouse ESCs, iPSCs, ECCs, and EpiSCs to form trophoblast. ESCs do not readily differentiate into trophoblast, but overexpression of the trophoblast-expressed transcription factor, CDX2, leads to efficient differentiation to trophoblast and to formation of trophoblast stem cells (TSCs) in the presence of fibroblast growth factor-4 (FGF4) and Heparin. Interestingly, we found that iPSCs and ECCs could both give rise to TSC-like cells following Cdx2 overexpression, suggesting that these cell lines are equivalent in developmental potential. By contrast, EpiSCs did not give rise to TSCs following Cdx2 overexpression, indicating that EpiSCs are no longer competent to respond to CDX2 by differentiating to trophoblast. In addition, we noted that culturing ESCs in conditions that promote naïve pluripotency improved the efficiency with which TSC-like cells could be derived. This work demonstrates that CDX2 efficiently induces trophoblast in more naïve than in primed pluripotent stem cells and that the pluripotent state can influence the developmental potential of stem cell lines.
authors.affiliation: 1Department of Molecular, Cell, and Developmental Biology, University of California Santa Cruz, Santa Cruz, California.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Blij
authors.affiliation: 2Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan.
authors.forename: Anthony
authors.initials: A
authors.lastname: Parenti
authors.affiliation: 1Department of Molecular, Cell, and Developmental Biology, University of California Santa Cruz, Santa Cruz, California.
authors.forename: Neeloufar
authors.initials: N
authors.lastname: Tabatabai-Yazdi
authors.affiliation: 2Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan.
authors.forename: Amy
authors.initials: A
authors.lastname: Ralston
mesh_terms: D000818:Animals; D000071616:CDX2 Transcription Factor; D002454:Cell Differentiation; D002460:Cell Line; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology*
chemical_list: D000071616:CDX2 Transcription Factor; C487514:Cdx2 protein, mouse; D018398:Homeodomain Proteins; D014157:Transcription Factors