Leukaemia inhibitory factor is identical to the myeloid growth factor human interleukin for DA cells

Abstract

Leukaemia inhibitory factor (LIF) is a cytokine that induces macrophage differentiation of the murine M1 myeloid leukaemia cell line. We have isolated a cDNA clone encoding a novel human haemopoietic growth factor, human interleukin for DA cells (HILDA) that supports the proliferation of the murine interleukin-3-dependent leukaemic cell line, DA-la (refs 3-5). HILDA proved to be identical to LIF. The demonstration that the differentiation factor LIF will also serve as a growth factor for at least one myeloid leukaemic cell line provides further evidence that the distinction between growth-promoting and differentiation-inducing activities are largely determined by the target cell type.

Developmental expression of myeloid leukemia inhibitory factor gene in preimplantation blastocysts and in extraembryonic tissue of mouse embryos.

“…TGF-P is already known to have two opposite effects on cell differentiation (3,14). Transcription of the LIF gene in the blastocyst and in the placenta of the midgestation embryo is consistent with the hypothesis that this factor has growth-promoting and differefitiation-inducing activities determined by the target cell type (15) (Fig. 2B).…”

“…It induces macrophage differentiation in the Ml murine myeloid leukemia cells and suppresses their proliferation (10,12), whereas it supports the proliferation of murine interleukin-3-dependent leukemic DA-la cells (15). In addition, it was recently demonstrated that LIF is identical to the cholinergic neuronal differentiation factor from heart cells (24).…”

“…The LIF gene is transcribed by the blastocyst but not by ES cells, which most closely resemble early ICM cells (2). Taking into account also the presence of an LIF-specific membrane receptor on ES cells (21,23) and LIF direct action on the maintenance of the pluripotent state of those cells (15,21,23), it is reasonable to think that transcription may occur in the trophectoderm and that the molecule acts on the ICM cells. Further studies in progress in our laboratory with antibodies to LIF protein will be needed to confirm this reverse interaction between tissues.…”

Synthesis, Cytotoxic Properties and Effects on Early and Late Gene Induction of a Chimeric Diphtheria Toxin‐Leukemia‐Inhibitory Factor Protein

“…Although the mouse LIF gene has been cloned (Mereau et al, 1993), the human LIF gene was used in the present fusion protein construct, as human LIF is also active on mouse cells (Moreau et al, 1988) while the mouse protein is Iess active on human cells (Owczarek et al, 1993). Deletions at the C-terminus of the LIF sequence in DT-(1-389)-LIF-(2-184)-peptide abolished its cytotoxic action.…”

Identification of CpG island at the 5' end of murine leukemia inhibitory factor gene

“…LIF is known to have distinct in vitro activities. It induces macrophage differentiation in the Ml murine myeloid leukemia cells and suppresses their proliferation [l], it supports the proliferation of murine interleukin-3-dependent leukemic DA-1 a cells [2] and inhibits differentiation of embryonic stem cells [3]. Furthermore, LIF promotes bone resorption in vitro [4].…”