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      Conversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture.

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          Abstract

          Mouse embryonic stem (ES) cells are competent for production of all fetal and adult cell types. However, the utility of ES cells as a developmental model or as a source of defined cell populations for pharmaceutical screening or transplantation is compromised because their differentiation in vitro is poorly controlled. Specification of primary lineages is not understood and consequently differentiation protocols are empirical, yielding variable and heterogeneous outcomes. Here we report that neither multicellular aggregation nor coculture is necessary for ES cells to commit efficiently to a neural fate. In adherent monoculture, elimination of inductive signals for alternative fates is sufficient for ES cells to develop into neural precursors. This process is not a simple default pathway, however, but requires autocrine fibroblast growth factor (FGF). Using flow cytometry quantitation and recording of individual colonies, we establish that the bulk of ES cells undergo neural conversion. The neural precursors can be purified to homogeneity by fluorescence activated cell sorting (FACS) or drug selection. This system provides a platform for defining the molecular machinery of neural commitment and optimizing the efficiency of neuronal and glial cell production from pluripotent mammalian stem cells.

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          Author and article information

          Journal
          Nat Biotechnol
          Nature biotechnology
          Springer Science and Business Media LLC
          1087-0156
          1087-0156
          Feb 2003
          : 21
          : 2
          Affiliations
          [1 ] Institute for Stem Cell Research, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh EH9 3JQ, United Kingdom.
          Article
          nbt780
          10.1038/nbt780
          12524553
          2bae81fc-7059-4305-b27a-b94d29286c13
          History

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