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The unsolved enigmas of leukemia inhibitory factor
1Division of Cancer and Haematology, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. metcalf@wehi.edu.au
Insights
Leukemia inhibitory factor (LIF) is a versatile cytokine crucial for embryonic stem cell pluripotency and development. Its broad functions and complex regulation present ongoing research challenges.
Area of Science:
- Biochemistry
- Cell Biology
- Developmental Biology
Background:
- Leukemia inhibitory factor (LIF) is a glycoprotein cytokine with broad biological functions.
- LIF mediates its effects through a heterodimeric receptor involving LIFR and gp130.
- It plays critical roles in early development, including blastocyst implantation and neurogenesis.
Purpose of the Study:
- To review the diverse roles and mechanisms of Leukemia inhibitory factor (LIF).
- To highlight LIF's importance in experimental biology, particularly for maintaining embryonic stem cell totipotency.
- To discuss the unresolved questions regarding LIF's induction and its widespread regulatory roles.
Main Methods:
- Literature review and synthesis of existing research on Leukemia inhibitory factor (LIF).
- Analysis of LIF's molecular interactions and signaling pathways.
- Examination of LIF's physiological and experimental applications.
Main Results:
- LIF is involved in numerous processes including hematopoiesis, bone formation, and neuronal development.
- Embryonic stem cells utilize LIF to maintain their totipotentiality.
- Strategies exist to mitigate unwanted LIF activity, such as soluble receptors and SOCS proteins.
Conclusions:
- LIF is a pleiotropic cytokine with essential roles in development and cellular regulation.
- Further research is needed to elucidate the mechanisms controlling LIF induction and its diverse biological applications.
- Understanding LIF's complex signaling is key for its therapeutic and experimental utilization.
Abstract:
Leukemia inhibitory factor (LIF) is a polyfunctional glycoprotein cytokine whose inducible production can occur in many, perhaps all, tissues. LIF acts on responding cells by binding to a heterodimeric membrane receptor composed of a low-affinity LIF-specific receptor and the gp130 receptor chain also used as the receptor for interleukin-6, oncostatin M, cardiotrophin-1, and ciliary neurotrophic factor. LIF is essential for blastocyst implantation and the normal development of hippocampal and olfactory receptor neurons. LIF is used extensively in experimental biology because of its key ability to induce embryonic stem cells to retain their totipotentiality. LIF has a wide array of actions, including acting as a stimulus for platelet formation, proliferation of some hematopoietic cells, bone formation, adipocyte lipid transport, adrenocorticotropic hormone production, neuronal survival and formation, muscle satellite cell proliferation, and acute phase production by hepatocytes. Unwanted actions of LIF can be minimized by circulating soluble LIF receptors and by intracellular suppression by suppressors of cytokine-signaling family members. However, the outstanding problems remain of how the induction of LIF is mediated in response to demands from such a heterogeneity of target tissues and why it makes design sense to use LIF in the regulation of such a diverse and unrelated series of biological processes.
