K_Saili_Molecular characterization of a toxicological tipping point during human stem cell differentiation

We differentiated human induced pluripotent stem cells (hiPSCs) to embryonic endoderm and sought to identify a tipping point at which the developing system did not recover from perturbations caused by exposure to a known teratogen, all-trans retinoic acid (ATRA). Differentiating iPSC-derived endoderm was exposed to five concentrations of ATRA between 0.001 and 10 µM at 6h, 96h, or 192h and assessed for forkhead box A2 (FOXA2) protein expression and global gene transcript expression measured by RNA-sequencing. A tipping point of 17±11 nM was identified where patterns of differentially expressed genes supported a shift in the developmental trajectory away from embryonic endoderm in favor of mesoderm and extraembryonic endoderm. Five concentrations of all-trans retinoic acid (ATRA) between 0.001 and 10 µM were compared to time-matched 0.1% DMSO controls at three timepoints (6h, 96h, and 192h) in differentiating endoderm. Two biological replicates were used. Undifferentiated controls (not in DMSO) were also included in duplicate as internal controls for 6h, 96h, and 144h. This dataset is associated with the following publication: Saili, K., T. Antonijevic, T. Zurlinden, I. Shah, C. Deisenroth, and T. Knudsen. Molecular characterization of a toxicological tipping point during human stem cell differentiation. REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 91(January 2020): 1-13, (2020).

                                            [
  "020:00"
]
                                        

                                            {
  "fn": "Thomas Knudsen",
  "hasEmail": "mailto:knudsen.thomas@epa.gov"
}
                                        

                                            [
  {
    "title": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE131921",
    "accessURL": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE131921"
  }
]
                                        

                                            [
  "EOMES",
  "SOX17",
  "all-trans retinoic acid",
  "differentiation",
  "endoderm",
  "hiPSC",
  "tipping points",
  "vEmbryo",
  "virtual embryo",
  "virtual tissues"
]
                                        

                                            [
  "020:095"
]
                                        

                                            {
  "name": "U.S. EPA Office of Research and Development (ORD)",
  "subOrganizationOf": {
    "name": "U.S. Environmental Protection Agency",
    "subOrganizationOf": {
      "name": "U.S. Government"
    }
  }
}
                                        

                                            [
  "https://doi.org/10.1016/j.reprotox.2019.10.001"
]
                                        

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