Access

Letters to Nature

Nature 336, 688-690 (15 December 1988) | doi:10.1038/336688a0; Accepted 21 October 1988

Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides

Austin G. Smith*, John K. Heath*†, Deborah D. Donaldson‡, Gordon G. Wong‡, J. Moreau§, Mark Stahl‡ & David Rogers‡

  1. *Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
  2. ‡Genetics Institute, 87 Cambridge Park Drive, Cambridge, Boston, Massachusetts 02140, USA
  3. §INSERM U211, 1 Rue Gaston-Veil, 44035 Nantes, Cedex France
  4. †To whom correspondence should be addressed.
Top

Murine embryonic stem (ES) cells are pluripotent cell lines established directly from the early embryo1,2 which can contribute differentiated progeny to all adult tissues, including the germ-cell lineage3, after re-incorporation into the normal embryo. They provide both a cellular vector for the generation of transgenic animals4 and a useful system for the identification of polypeptide factors controlling differentiation processes in early development5. In particular, medium conditioned by Buffalo rat liver cells contains a polypeptide factor, ES cell differentiation inhibitory activity (DIA), which specifically suppresses the spontaneous differentiation of ES cells in vitro, thereby permitting their growth as homogeneous stem cell populations in the absence of heterologous feeder cells6. ES cell pluripotentiality, including the ability to give rise to functional gametes, is preserved after prolonged culture in Buffalo rat liver media as a source of DIA7. Here, we report that purified DIA is related in structure and function to the recently identified haemopoetic regulatory factors human interleukin for DA cells8,9 and leukaemia inhibitory factor10. DIA and human interleukin DA/leukaemia inhibitory factor have thus been identified as related multifunctional regulatory factors with distinct biological activities in both early embryonic and haemopoetic stem cell systems.