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Leukemia inhibitory factor (LIF).

Nicos A Nicola1, Jeffrey J Babon1

  • 1The Walter and Eliza Hall Institute of Medical Research, 1G Royal Pde, Parkville, Melbourne 3052, VIC, Australia; Department of Medical Biology, University of Melbourne, Royal Pde, Melbourne 3050, VIC, Australia.

Cytokine & Growth Factor Reviews
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Summary
This summary is machine-generated.

Leukemia inhibitory factor (LIF), a versatile cytokine, exhibits diverse effects on cell behavior. Its crucial roles in development and stem cell maintenance highlight its significance.

Keywords:
Embryonic stem cellsJAK/STAT/SOCSLIF receptorLeukemia inhibitory factorNerve and musclePregnancy

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Area of Science:

  • Cell Biology
  • Developmental Biology
  • Immunology

Background:

  • Leukemia inhibitory factor (LIF) is a highly pleiotropic cytokine within the interleukin-6 family.
  • LIF shares its receptor complex (LIFRβ/gp130) with other cytokines like CNTF, oncostatin M, CT1, and CLC.
  • Despite common signaling pathways (JAK/STAT, MAPK, PI3K), LIF elicits opposing cellular responses, affecting proliferation, differentiation, and survival.

Purpose of the Study:

  • To elucidate the multifaceted roles of Leukemia inhibitory factor (LIF) in cellular processes and development.
  • To investigate the non-redundant functions of LIF, particularly in reproduction and neurodevelopment.
  • To highlight the application of LIF in maintaining the pluripotency of stem cells.

Main Methods:

  • Review of existing literature on Leukemia inhibitory factor (LIF) and its signaling pathways.
  • Analysis of data from LIF knockout mouse models to identify essential functions.
  • Examination of LIF's role in embryonic stem cell and induced pluripotent stem cell culture.

Main Results:

  • LIF exhibits context-dependent effects, paradoxically influencing cell proliferation, differentiation, and survival.
  • LIF knockout mice show that many LIF functions are not essential for normal development but are induced during injury.
  • LIF plays critical, non-redundant roles in blastocyst implantation, placental formation, and nervous system development.

Conclusions:

  • LIF is a key regulator with diverse biological activities, essential for specific developmental processes and stem cell applications.
  • The context-dependent and often induced nature of LIF's functions underscores its specialized roles in tissue repair and early development.
  • LIF's ability to maintain pluripotency in stem cells is a significant finding with therapeutic implications.