Thursday, 6 June 2013

TERF1 is crucial for the generation of induced pluripotent stem cells

In a recent study, a team of researchers at the Spanish National Cancer Research Centre (CNIO), led by Ralph Schneider, and the Telomeres and Telomerase Group, headed by María Blasco, discovered that the TERF1 gene is both essential for the generation of induced pluripotent stem cells and can be used as a marker for pluripotenty.

The TERF1 gene (also known as TRF1) is a necessary component that protects the telomeres, the chromosome ends. TERF1 deficiency leads to early embryonic lethality and severe organ atrophy in adult tissues. Previous studies indicate that there is a strong relation between the length of telomeres and pluripotency, the capacity of a cell to differentiate into other types of cells. For instance, CNIO researchers have previously found that most pluripotent cells have very long telomeres. However, they had failed to identify a specific protein that protects telomeres, helping them to retain their pluripotency.

Human chromosomes (grey) capped by telomeres (white)

In their investigation to find a connection between telomeres and pluripotency, the research team developed "a reporter mouse".

"We generated a reporter mouse carrying a knock-in eGFP-TRF1 fusion allele to study the role of TRF1 in stem cell biology and tissue homeostasis." an extract from the study.

Essentially, they linked together the TERF1 gene along with a gene that codes a green fluorescent protein and created a lineage of mice carrying this new genetic baggage, using the the green fluorescent protein to mark the expression of TERF1.

They later found that TERF1 is an excellent marker for many types of stem cells, including adult, embryonic and induced pluripotent stem cells. TERF1 distinguishes adult stem cells and is indispensable for their functioning, said the researchers, adding that their discovery can be used to identify and isolate pluripotent stem cells from tissues, which is crucial for advancing regenerative medicine. The same applies for induced pluripotent stem cells, they said.

"The expression of TERF1 is an indicator of pluripotency. Those iPS cells that express the highest levels of TERF1 are also the most pluripotent. Furthermore, we demonstrate that TERF1 is necessary for the induction and maintenance of pluripotency, inhibiting the triggering of DNA damage responses and apoptosis ('cell suicide')."said the researchers.

Schneider, R., Garrobo, I., Foronda, M., Palacios, J., Marión, R., Flores, I., Ortega, S., & Blasco, M. (2013). TRF1 is a stem cell marker and is essential for the generation of induced pluripotent stem cells Nature Communications, 4 DOI: 10.1038/ncomms2946

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