LIN28 is thought to regulate the self-renewal of stem cells. In Caenorhabditis elegans, there is only one Lin28 gene that is expressed and in vertebrates, there are two paralogs present, Lin28a and Lin28b. In nematodes, the LIN28 homolog lin-28 is a heterochronic gene that determines the onset of early larval stages of developmental events in C. elegans, by regulating the self-renewal of nematode stem cells in the skin (called seam cells) and vulva (called VPCs) during development. In mice, LIN28 is highly expressed in mouse embryonic stem cells and during early embryogenesis.
LIN28 is highly expressed in human embryonic stem cells and can enhance the efficiency of the formation of induced pluripotent stem (iPS) cells from human fibroblasts.
LIN28 can regulate glucose homeostasis in mammals by increasing insulin-PI3K-mTOR signaling and insulin sensitivity, thereby promoting resistance to high fat diet-induced obesity and type 2 diabetes. Aberrant expression of LIN28 has been seen to regulate aerobic glycolysis to facilitate cancer proliferation
Mice genetically altered to produce LIN28 during their lifespan showed improved hair growth. and healthy tissue regeneration on added puncture wounds in later life stages. While the mice could regenerate limbs, they could not repair damaged heart tissue. Appropriate drugs replicated the regeneration in unaltered mice, using the same metabolic paths. The drugs increased the subjects' metabolic rates, evidently causing the body to heal at higher rates. The effects of Lin28a activation faded with age.
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