Blackshear, Perry (NIEHS)
Embryonic stem cells (ESCs) are pluripotent cells that can be cultured indefinitely, and maintain their capability to differentiate into all cell lineages. To maintain these cells as well as various types of related induced stem cells and progenitor cells in culture, Mouse Embryonic Fibroblasts (MEFs) are routinely used as feeder cells, largely to serve as a source of Leukemia Inhibitory Factor (LIF). ESCs can also be cultured without feeders if the medium is supplemented with recombinant LIF and other factors. However, these methods of culturing ESCs suffer from certain drawbacks, such as limited proliferation capacity and variability of primary MEFs. Therefore, finding improved conditions that maintain ESC pluripotency is an area of great interest.
Scientists at NIEHS have now developed a knock-in (KI) mouse model in which LIF is overproduced from its endogenous locus because of increased stability of its mRNA. MEFs and presumably other cells derived from the homozygous mice hypersecrete LIF protein; lesser degrees of overexpression would be expected from heterozygous mice. These mice can be used to study LIF function, including how LIF contributes to various physiological and pathological states. Cells derived from these mice can be used to culture ESCs, as well as other progenitor cells. Cells or genetic material derived from these mice can also be used as sources of LIF for isolation and purification.
- Maintenance of ESCs and progenitor cells
- In vivo, cellular and cell-free sources of LIF
- Sources of LIF for isolation and purification
- Studies of LIF function in mice, such as contribution of LIF to tumor growth