Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells

@article{Williams1988MyeloidLI,
  title={Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells},
  author={R. L. Williams and Douglas J. Hilton and Shirley Pease and Tracy A. Willson and Colin L Stewart and David P. Gearing and Erwin F. Wagner and Donald Metcalf and Nicos A. Nicola and N. M. Gough},
  journal={Nature},
  year={1988},
  volume={336},
  pages={684-687}
}
Embryonic stem (ES) cells, the totipotent outgrowths of bias-tocysts1,2, can be cultured and manipulated in vitro and then returned to the embryonic environment where they develop normally and can contribute to all cell lineages3–9. Maintenance of the stem-cell phenotype in vitro requires the presence of a feeder layer of fibroblasts1,2,10 or of a soluble factor, differentiation inhibitory activity (DIA) produced by a number of sources5,11,12; in the absence of DIA the ES cells differentiate… 
Self renewal of embryonic stem cells in the absence of feeder cells and exogenous leukaemia inhibitory factor.
TLDR
It is suggested that the signalling pathway involving diffusible LIF can be bypassed for maintaining the pluripotency in culture, and a considerable heterogeneity in growth factor dependence and differentiation of different ES cells is indicated.
Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides
TLDR
DIA and human interleukin DA/leukaemia inhibitory factor have been identified as related multifunctional regulatory factors with distinct biological activities in both early embryonic and haemopoetic stem cell systems.
Leukaemia inhibitory factor is necessary for maintenance of haematopoietic stem cells and thymocyte stimulation
TLDR
It is shown that LIF-deficient mice derived by gene targeting techniques have dramatically decreased numbers of stem cells in spleen and bone marrow, suggesting that stem cells interact differently with the splenic and medullary microenvironment.
Use of avian cytokines in mammalian embryonic stem cell culture.
TLDR
Results indicate that avian cells can produce a LIF-like cytokine that is active in inhibiting the differentiation of mouse ES cells, which could provide a biological end point for the isolation and characterization of avian LIF.
Characteristics of embryonic stem cell differentiation: a comparison with two embryonal carcinoma cell lines.
Paracrine induction of stem cell renewal by LIF-deficient cells: a new ES cell regulatory pathway.
TLDR
It is established that ES cell pluripotency can be sustained via a LIF-R/gp130-independent, STAT-3 independent, signaling pathway and Operation of this pathway in vivo could play an important role in the regulation of pluripOTency in the epiblast and account for the viability of lifr and gp130 -/- embryos.
Embryonic Stem Cells Release Potentially Novel Hematopoietic Factors
TLDR
The results offer a new approach for the identification of factors implicated in stem cell proliferation, self-renewal and commitment and the improved LTC conditions for the expansion of stem cells without reduction of their in vitro differentiation potential should be useful for a wide range of applications.
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References

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Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides
TLDR
DIA and human interleukin DA/leukaemia inhibitory factor have been identified as related multifunctional regulatory factors with distinct biological activities in both early embryonic and haemopoetic stem cell systems.
Molecular cloning and expression of cDNA encoding a murine myeloid leukaemia inhibitory factor (LIF).
TLDR
Cloning, sequencing and expressing LIF has resolved several discrepancies in the literature concerning the identity of factors capable of inducing differentiation of murine myeloid leukaemic cells in vitro.
Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells.
  • G. Martin
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1981
TLDR
The establishment directly from normal preimplantation mouse embryos of a cell line that forms teratocarcinomas when injected into mice makes feasible the isolation of pluripotent cells lines from various types of noninbred embryo, including those carrying mutant genes.
Clonal analysis of the actions of the murine leukemia inhibitory factor on leukemic and normal murine hemopoietic cells.
TLDR
The differing actions of LIF and G-CSF on M1 leukemic cells suggest the existence of distinct mechanisms for inducing macrophage differentiation in these leukeMIC cells.
The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium.
TLDR
The in vitro developmental potential of mouse blastocyst-derived embryonic stem cell lines and the consistency with which the cells express this potential are presented as aspects which open up new approaches to the investigation of embryogenesis.
HPRT-deficient (Lesch–Nyhan) mouse embryos derived from germline colonization by cultured cells
TLDR
The realization of this possibility by the selection in vitro of variant ES cells deficient in hypoxanthine guanine phosphoribosyl transferase is reported, leading to their use to produce germline chimaeras resulting in female offspring heterozygous for HPRT-deficiency, and the generation of HPRt-deficient preimplantation embryos from these females.
Structural characterization of a murine myeloid leukaemia inhibitory factor.
A leukaemia inhibitory factor (LIF) which induces macrophage differentiation in M1 murine myeloid leukaemia cells and suppresses their proliferation in vitro has been isolated in sufficient
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