Key protein reveals secret of stem cell pluripotency

Sep 06, 2011
Diagram of the Ccl2 and leukemia inhibitory factor (LIF) signal pathways integrating into the transcription network. Known LIF signal pathway is shown with black arrow. Our finding of Ccl2 signal pathway for promoting pluripotency is shown as dot black arrow. Abbreviations: IL-6R, interleukin-6 receptor; LIF, leukemia inhibitory factor; LIFR, leukemia inhibitory factor receptor; NC, negative control; PI(3)K, phosphoinositide 3-kinase. Credit: RIKEN

A protein that helps maintain mouse stem cell pluripotency has been identified by researchers at the RIKEN Omics Science Center. The finding, published in the August issue of Stem Cells (first published online July 26, 2011), points the way to advances in regenerative medicine and more effective culturing techniques for human pluripotent stem cells.

Through their capacity to differentiate into any other type of cell, (ES ) and induced-pluripotent (iPS cells) promise a new era of cell-based treatments for a wide range of conditions and diseases. Cultivating such cells, however, commonly relies on the use of so-called “feeder” cells to maintain in cell culture conditions. Feeder cells keep stem cells in their undifferentiated state by releasing nutrients into the culture medium, but they have the potential to introduce contamination which, in humans, can lead to serious health risks.

Previous research has shown that mouse 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 discovered early in their investigation, however, that the amount of LIF secreted from feeder cells is much less than the amount needed to maintain pluripotency in feeder-free conditions. This points to other, as-of-yet unknown contributing factors.

To clarify these factors, 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.

While CCL2 is known for its role in recruiting certain cells to sites of infection or inflammation, the current research is the first to demonstrate that it also helps maintain iPS cell pluripotency. The findings also offer broader insights applicable to the cultivation of human iPS/ES cells, setting the groundwork for advances in regenerative medicine.

Explore further: Fighting bacteria—with viruses

More information: Yuki Hasegawa, et al. "CC Chemokine Ligand 2 and Leukemia Inhibitory Factor Cooperatively Promote Pluripotency in Mouse Induced Pluripotent Cells." Stem Cells, 2011, DOI: 10.1002/stem.673

add to favorites email to friend print save as pdf

Related Stories

Recommended for you

Fighting bacteria—with viruses

Jul 24, 2014

Research published today in PLOS Pathogens reveals how viruses called bacteriophages destroy the bacterium Clostridium difficile (C. diff), which is becoming a serious problem in hospitals and healthcare institutes, due to its re ...

Atomic structure of key muscle component revealed

Jul 24, 2014

Actin is the most abundant protein in the body, and when you look more closely at its fundamental role in life, it's easy to see why. It is the basis of most movement in the body, and all cells and components ...

Brand new technology detects probiotic organisms in food

Jul 23, 2014

In the food industr, ity is very important to ensure the quality and safety of products consumed by the population to improve their properties and reduce foodborne illness. Therefore, a team of Mexican researchers ...

Protein evolution follows a modular principle

Jul 23, 2014

Proteins impart shape and stability to cells, drive metabolic processes and transmit signals. To perform these manifold tasks, they fold into complex three-dimensional shapes. Scientists at the Max Planck ...

Report on viruses looks beyond disease

Jul 22, 2014

In contrast to their negative reputation as disease causing agents, some viruses can perform crucial biological and evolutionary functions that help to shape the world we live in today, according to a new report by the American ...

User comments : 0