Stem Cell Pluripotency Tied To Key Protein

Embryonic stem cells (ES cells) and induced-pluripotent stem cells (iPS cells) promise a new era of cell-based treatments for a wide range of conditions and diseases. They do this through their capacity to differentiate into any other type of cell.

Cultivating such cells has relied on the use of so-called "feeder" cells to maintain pluripotency in cell culture conditions. Feeder cells keep stem cells in their undifferentiated state by releasing nutrients into the culture medium. But they also have the potential to introduce contamination which, in humans, can lead to serious health risks.

Now a protein that helps maintain mouse stem cell pluripotency has been identified by researchers at the RIKEN Omics Science Center.

Previous research showed that mouse pluripotent stem cells can be cultured without feeder cells through the addition of a cytokine called Leukemia Inhibitory Factor (LIF) to the culture media ("feeder-free" culture). LIF is secreted by mouse feeder cells and activates signal pathways reinforcing a stem cell regulatory network.

The researchers found that the amount of LIF secreted from feeder cells is much less than the amount needed to maintain pluripotency in feeder-free conditions which pointed to other, as-of-yet unknown contributing factors.

To clarify, the research group analyzed differences in gene expression between mouse iPS cells cultured on feeder cells and those cultured in feeder-free (LIF treated) conditions. Their results revealed 17 genes whose expression level is higher in feeder conditions. To test for possible effects on pluripotency, they then selected 7 chemokines (small proteins secreted by cells) from among these candidates and overexpressed them in iPS cells grown in feeder-free conditions. They found that one chemokine in particular, CC chemokine ligand 2 (CCL2), enhances the expression of key pluripotent genes via activation of a well-known signal pathway known as Jak/Stat3.

CCL2 is known for its role in recruiting certain cells to sites of infection or inflammation. However this research is the first to demonstrate that it also helps maintain iPS cell pluripotency.

Adapted from the RIKEN Omics Science Center announcement.