LIF/STAT3 Signaling Fails to Maintain Self-Renewal of Human Embryonic Stem Cells

Authors

  • Laurence Dahéron,

    1. Whitehead Institute for Biomedical Research, Cambridge, and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Division of Pediatric Hematology/Oncology, The Children's Hospital and Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Search for more papers by this author
  • Sarah L. Opitz,

    1. Whitehead Institute for Biomedical Research, Cambridge, and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Division of Pediatric Hematology/Oncology, The Children's Hospital and Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Search for more papers by this author
  • Holm Zaehres,

    1. Whitehead Institute for Biomedical Research, Cambridge, and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Division of Pediatric Hematology/Oncology, The Children's Hospital and Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Search for more papers by this author
  • William M. Lensch,

    1. Whitehead Institute for Biomedical Research, Cambridge, and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Division of Pediatric Hematology/Oncology, The Children's Hospital and Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Search for more papers by this author
  • Peter W. Andrews,

    1. Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield, United Kingdom
    Search for more papers by this author
  • Joseph Itskovitz-Eldor,

    1. Technion University, Rambam Medical Center, Haifa, Israel
    Search for more papers by this author
  • George Q. Daley M.D., Ph.D.

    Corresponding author
    1. Whitehead Institute for Biomedical Research, Cambridge, and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Division of Pediatric Hematology/Oncology, The Children's Hospital and Dana Farber Cancer Institute, Boston, Massachusetts, USA
    • Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA. Telephone: 617-919-2013; Fax: 617-730-0222
    Search for more papers by this author

Abstract

Murine embryonic stem (mES) cells remain undifferentiated in the presence of leukemia inhibitory factor (LIF), and activation of signal transducer and activator of transcription 3 (STAT3) via LIF receptor (LIFR) signaling appears sufficient for maintenance of mES cell pluripotency. Anecdotal and contradictory accounts exist for the action of LIF in the culture of human embryonic stem cells, and the nature of LIF signaling and whether the LIF-STAT3 pathway is conserved in human embryonic stem cells (hESCs) has not been systematically explored. In this study, we show that the LIFRβ and the signaling subunit gp130 are expressed in hESCs and that human LIF can induce STAT3 phosphorylation and nuclear translocation in hESCs. Nevertheless, despite the functional activation of the LIF-STAT3 signaling pathway, human LIF is unable to maintain the pluripotent state of hESCs. Feeder-free culture conditions that maintain hESCs in an undifferentiated state do not show activation of STAT3, suggesting that distinct signaling mechanisms govern the self-renewal of hESCs.

Ancillary