It is well known that primary cells only undergo a predetermined and finite number of cell divisions in culture. After limited population doublings (the number of which varies by species, cell type, and culture conditions), primary cells enter a state called replicative senescence, where they can no longer divide. To surpass senescence, several methods exist for immortalizing mammalian cells in culture. The most recently discovered approach to cell immortalization is through the expression of Telomerase Reverse Transcriptase protein (TERT). It is particularly useful for cells that are most affected by telomere length, including many human cell types. This protein is usually silenced in most somatic cells. These cells can avoid replicative senescence by maintaining sufficient telomere lengths when hTERT is exogenously introduced. However, over-expression of hTERT in some cell types (especially in epithelial cells) fails to induce cell immortalization.