Stem cells’ line of defenses

NUS biological scientists have identified the genes responsible for defending stem cells against viral infections.

Stem cells are cells that are capable of differentiating into various functional cells in the body. Hence, the discovery of these cells has paved the way for the advancement of regenerative medicine. Stem cells are known to defend themselves against viruses in order to protect the developing organism from harmful and lethal diseases. Exactly how stem cells do this was previously unknown.

A research team led by Prof Jonathan LOH from the Department of Biological Sciences in NUS has identified the genes responsible for the suppression of viral infections in stem cells by using a powerful genomic screening technology. In order to use stem cells in regenerative medicine, they have to be produced in large-scale and in high quality. These cells have to be identical to the stem cells found in the body. As the defence against viruses is an essential trait that stem cells have, identifying the mechanism by which these cells repress viruses becomes crucial for producing high quality stem cells.

This study is the first to apply genomic screening technologies to identify all the genes responsible for defending stem cells against viruses. Reported genes were identified in the screen along with many novel genes not known before to have a role in this biological phenomenon.

The research team is working on the identification of the functional interplay networks among all these genes, which is crucial to repress viral infections in stem cells. They also intend to explore how the mis-regulation of genomic viral elements can lead to diseases such as cancer. This study has provided valuable information on the genes which need to be tested for the role they play in preventing the expression of viral elements and hence the defence against cancer.

Figure shows microscope images of stem cells infected with viruses tagged with a green protein (GFP). The control image (siNT, normal stem cells) shows no green colour because the viruses are repressed. The other images show green colour because in each image a gene responsible for viral repression is not allowed to be expressed (e.g. reducing expression of Ube2i gene, siUbe2i, allows viruses to infect stem cells). Used with permission from Elsevier (License No. 3870301090878).

Reference

Yang BX, El Farran CA, Guo HC, Yu T, Fang HT, Wang HF, Schlesinger SS, Yu Fen S, Goh GYL, Neo SP, Li Y, Lorincz MC, Tergaonkar V, Lim TM, Chen L, Gunaratne J, Collins JJ, Goff SP, Daley GQ, Li H, Bard FA, Loh YH. “Systematic Identification of Factors for Provirus Silencing in Embryonic Stem Cells”. Cell. 163 (2015) 230-245.