Transgenic expression of Telomerase reverse transcriptase (Tert) improves cell proliferation of primary cells and enhances reprogramming efficiency into the induced pluripotent stem cell.
The enzymatic activity of telomerase is important for the extension of the telomere repeat sequence and overcoming cellular senescence. We generated a conditional transgenic mouse line, carrying the telomerase reverse transcriptase (Tert) expression cassette, controlled by the Cre-loxP-mediated recombination. In our study, Cre recombinase expression efficiently activated Tert expression, resulting in its increased enzymatic activity, which extended the period of cellular proliferation until the keratinocytes entered senescence. This suggests that transgenic Tert expression is effective in enhancing primary cell proliferation. Notably, Tert expression increased colony formation of induced pluripotent stem (iPS) cells after the introduction of four reprogramming factors, Oct-4, klf4, SOX-2, and c-Myc into the transgenic fibroblasts. To the best of our knowledge, this is the first study to show that the transgenic Tert expression enhances reprogramming efficiency of iPS cells, which indicates a critical role for Tert in the reprogramming process.
a Graduate School of Agricultural Science , Tohoku University , Sendai , Japan.
Shizu
S
Hidema
a Graduate School of Agricultural Science , Tohoku University , Sendai , Japan.
Tomokazu
T
Fukuda
a Graduate School of Agricultural Science , Tohoku University , Sendai , Japan.
Shiori
S
Date
b Cell Resource Center for Biomedical Research, Institute of Development, Aging, and Cancer , Tohoku University , Sendai , Japan.
Yuko
Y
Tokitake
b Cell Resource Center for Biomedical Research, Institute of Development, Aging, and Cancer , Tohoku University , Sendai , Japan.
Yasuhisa
Y
Matsui
c Department of Translational Oncology , National Cancer Center Research Institute , Tokyo , Japan.
Hiroki
H
Sasaki
a Graduate School of Agricultural Science , Tohoku University , Sendai , Japan.
Katsuhiko
K
Nishimori
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D065150:Cellular Reprogramming; D015870:Gene Expression; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D019426:Integrases / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D051379:Mice; D008822:Mice, Transgenic; D019098:Telomerase / Q000235:genetics*
C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; C045073:Cre recombinase; D019426:Integrases; D019098:Telomerase
keratinocyte; primary cell; proliferation; reprogramming; telomerase