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May 26, 2011

ECAT11 is expressed in the initial stage of iPS cell induction

A group of researchers, led by Keisuke Okita, a lecturer at the Center for iPS Cell Research and Application (CiRA), Kyoto University, have discovered that ECAT11 (L1td1), one factor specifically expressed in embryonic stem (ES) cells, is expressed at an extremely early stage of induced pluripotent stem (iPS) cell induction although the factor is not essential for the maintenance of pluripotency of mice ES cells. The findings were published in the American science journal, "PLoS ONE."

ES cells have the ability for both high proliferation and differentiation into various cells in the body, the properties that iPS cells have. The research team focused on one factor that is specifically expressed in ES cells, ECAT11, and analyzed its functions.

When an ECAT11 knockout mouse, in which EGFP (fluorescent protein) is expressed instead of ECAT11, was produced, it grew in the same way as an ordinary mouse, with no specific abnormalities being observed. Moreover, there were no changes observed in the proliferative capacity and differentiation capability with normal ES cells when ECAT11-null ES cells were produced. This result shows that ECAT11 is not essential for ontogenesis as well as the maintenance of pluripotency in the cells.

When the researchers analyzed the expression-controlling mechanism of ECAT11 in the process of inducing iPS cells, they found that the expression of ECAT11 is only activated when Oct3/4, Sox2 and Klf4, three inducing factors of iPS cells, were simultaneously expressed in mice fibroblasts. In addition, the research reveals that the expression of ECAT11 starts at an extremely early stage of iPS cell induction.

The team produced the ECAT11-EGFP fluorescent reporter, in which EGFP is expressed instead of ECAT11. From the fact that it only glows in the very initial period of the iPS cell induction process, it is believed that the ECAT11-EGFP fluorescent reporter is useful in analyzing the reprogramming mechanism of iPS cells.

"ECAT11/Ltd1 is enriched in ES cells and rapidly activated during iPS cell generation, but it is dispensable for the maintenance and induction of pluriopotency"
Kumiko A. Iwabuchi, Tatsuya Yamakawa, Yoshiko Sato, Tomoko Ichisaka, Kazutoshi Takahashi, Keisuke Okita and Shinya Yamanaka.

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