Transgenic expression of Telomerase reverse transcriptase (Tert) improves cell proliferation of primary cells and enhances reprogramming efficiency into the induced pluripotent stem cell

Abstract

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.

Expression of the Reverse Transcriptase Domain of Telomerase Reverse Transcriptase Induces Lytic Cellular Response in DNA-Immunized Mice and Limits Tumorigenic and Metastatic Potential of Murine Adenocarcinoma 4T1 Cells

“…To delineate if this could be the case, we generated clones of murine mammary gland adenocarcinoma cell line 4T1luc2 expressing rtTERT and evaluated their in vitro properties and their potential to form tumors and metastasis upon implantation into syngenic BALB/c mice as compared to the parental cells. Of four 4T1luc2 clones made to express rtTERT, three had increased population of cells in S and G2/M phase areas indicative of enhanced cell proliferation, corroborating earlier findings of transgenic expression of TERT extending cell proliferation phase [ 70 ], a property which could thus be attributed to the expression of RT domain. Two of three clones with increased cell proliferation exhibited multiple foci formed by the phosphorylated form of H2A histone family member X (γ-H2AX foci; [ 59 ]), significantly exceeding their level in the parental cell line.…”

A Comparative Study of the Effect of Anatomical Site on Multiple Differentiation of Adipose-Derived Stem Cells in Rats

“…cell differentiation [ 53 ]. Additionally, Tert improves cell proliferation of primary cells and enhances reprogramming efficiency into the induced pluripotent stem cell [ 54 ].…”

Impact of Adipose Tissue Depot Harvesting Site on the Multilineage Induction Capacity of Male Rat Adipose-Derived Mesenchymal Stem Cells: An In Vitro Study

“…Rex-1 is an important stem cell marker that has a key role in the differentiation of embryonic stem cells [ 42 ]. Additionally, Tert is crucial for enhancing the growth of primary cells and boosting the efficacy of the reprogramming of the induced pluripotent stem cells [ 43 ]. As multipotent cells, MSCs exhibit an outstanding ability to be induced and differentiate into various cell lineages, such as adipogenic, osteogenic, and chondrogenic lineages.…”