Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides

Abstract

Murine embryonic stem (ES) cells are pluripotent cell lines established directly from the early embryo^1,2 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 cells^8,9 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.