Embryonic stem cells in a culture medium must stay undifferentiated and divide indefinitely. This pluripotent state is maintained by several enzymes, transcription factors, and RNA molecules. The enzyme telomerase is present at high levels in ES cells and adds telomeres, short DNA sequences at the end of chromosomes. This protects the chromosomes from damage and allows for cell renewal. Chromatin regulators, such as histone-modifying enzymes, turn off genes that encode regulators of differentiation. Several transcription factors are core regulators of the ES cell state–Oct4, Sox2, and Nanog. These factors activate genes leading to pluripotency and self-renewal while suppressing those leading to differentiation. The core regulators also activate genes encoding certain microRNAs. Some microRNAs allow cells to proliferate by regulating cell-cycle progression, and maintain the ES cell state.