title: Trophoblast lineage cells derived from human induced pluripotent stem cells.
abstract: BACKGROUND
  During implantation, the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomes a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient's placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing.
  
  
  RESULTS
  Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts.
  
  
  CONCLUSIONS
  Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503, USA. ying.chen@hc.msu.edu
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Gadisetti V R
authors.initials: GV
authors.lastname: Chandramouli
authors.forename: Jason G
authors.initials: JG
authors.lastname: Knott
authors.forename: Richard
authors.initials: R
authors.lastname: Leach
mesh_terms: D002454:Cell Differentiation; D049109:Cell Proliferation; D044127:Epigenesis, Genetic; D006801:Humans; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D059467:Transcriptome; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism
keywords: Human indcued pluripotent stem cells; Trophoblast lineage cells