Leukemia inhibitory factor
Encyclopedia
Leukemia inhibitory factor, or LIF, an interleukin 6
class cytokine
, is a protein
in cell
s that affects cell growth and development.
of myeloid leukemic
cells. Other properties attributed to the cytokine include: the growth promotion and cell differentiation of different types of target cells, influence on bone
metabolism
, cachexia
, neural development
, embryogenesis
and inflammation
. p53
regulated LIF has been shown to facilitate implantation in the mouse model and possibly in humans. It has been suggested that recombinant human LIF might help to improve the implantation rate in women with unexplained infertility.
(LIFR-α) which forms a heterodimer with a specific subunit common to all members of that family of receptors, the GP130 signal transducing subunit. This leads to activation of the JAK
/STAT
(Janus kinase/signal transducer
and activator of transcription
) and MAPK (mitogen
activated protein
kinase
) cascades
.
. As embryonic stem cells are derived from the inner cell mass at the blastocyst stage, removing them from the inner cell mass also removes their source of LIF.
, but they retain their proliferative potential or pluripotency. Therefore LIF is used in mouse embryonic stem cell
culture. It is necessary to maintain the stem cells in an undifferentiated state, however genetic manipulation of embryonic stem cells allows for LIF independent growth, notably overexpression of the gene Nanog
.
LIF is not required for culture of human embryonic stem cells.
Interleukin 6
Interleukin-6 is a protein that in humans is encoded by the IL6 gene.IL-6 is an interleukin that acts as both a pro-inflammatory and anti-inflammatory cytokine. It is secreted by T cells and macrophages to stimulate immune response, e.g. during infection and after trauma, especially burns or other...
class cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
, is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
in cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
s that affects cell growth and development.
Function
LIF derives its name from its ability to induce the terminal differentiationCellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
of myeloid leukemic
Myeloid leukemia
Myeloid leukemia is a type of leukemia affecting myeloid tissue.Types include:* Acute myeloid leukemia* Chronic myelogenous leukemia...
cells. Other properties attributed to the cytokine include: the growth promotion and cell differentiation of different types of target cells, influence on bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
, cachexia
Cachexia
Cachexia or wasting syndrome is loss of weight, muscle atrophy, fatigue, weakness, and significant loss of appetite in someone who is not actively trying to lose weight...
, neural development
Neural development
Neural development comprises the processes that generate, shape, and reshape the nervous system, from the earliest stages of embryogenesis to the final years of life. The study of neural development aims to describe the cellular basis of brain development and to address the underlying mechanisms...
, embryogenesis
Embryogenesis
Embryogenesis is the process by which the embryo is formed and develops, until it develops into a fetus.Embryogenesis starts with the fertilization of the ovum by sperm. The fertilized ovum is referred to as a zygote...
and inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
. p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
regulated LIF has been shown to facilitate implantation in the mouse model and possibly in humans. It has been suggested that recombinant human LIF might help to improve the implantation rate in women with unexplained infertility.
Binding/activation
LIF binds to the specific LIF receptorReceptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
(LIFR-α) which forms a heterodimer with a specific subunit common to all members of that family of receptors, the GP130 signal transducing subunit. This leads to activation of the JAK
Jak
Jak may refer to:*JAK, Jazakomu Allahu Khayran *JAK members bank, a Swedish interest-free bank*Janus kinase, an intracellular signaling molecule; component of the JAK-STAT signal system...
/STAT
STAT
STAT may mean:*STAT protein, the Signal Transducers and Activators of Transcription protein*Special Tertiary Admissions Test, a set of tests aimed at assessing the critical reasoning abilities of university applicants who lack other formal qualifications...
(Janus kinase/signal transducer
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
and activator of transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
) and MAPK (mitogen
Mitogen
A mitogen is a chemical substance that encourages a cell to commence cell division, triggering mitosis. A mitogen is usually some form of a protein.Mitogenesis is the induction of mitosis, typically via a mitogen....
activated protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
kinase
Kinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...
) cascades
Biochemical cascade
A biochemical cascade is a series of chemical reactions in which the products of one reaction are consumed in the next reaction. There are several important biochemical cascade reactions in biochemistry, including the enzymatic cascades, such as the coagulation cascade and the complement system,...
.
Expression
LIF is normally expressed in the trophectoderm of the developing embryo, with its receptor LIFR expressed throughout the inner cell massInner cell mass
In early embryogenesis of most eutherian mammals, the inner cell mass is the mass of cells inside the primordial embryo that will eventually give rise to the definitive structures of the fetus...
. As embryonic stem cells are derived from the inner cell mass at the blastocyst stage, removing them from the inner cell mass also removes their source of LIF.
Use in stem cell culture
Removal of LIF pushes stem cells toward differentiationCellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
, but they retain their proliferative potential or pluripotency. Therefore LIF is used in mouse embryonic stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
culture. It is necessary to maintain the stem cells in an undifferentiated state, however genetic manipulation of embryonic stem cells allows for LIF independent growth, notably overexpression of the gene Nanog
NANOG
The North American Network Operators' Group is an educational and operational forum for the coordination and dissemination of technical information related to backbone/enterprise networking technologies and operational practices. It runs meetings, talks, surveys, and an influential mailing list...
.
LIF is not required for culture of human embryonic stem cells.