ABSTRACT

Induced Pluripotent Stem Cell .............................................65 3.2.2 Ef—ciency and Kinetics of iPS Cell Reprogramming......................... 71

3.3 Characterization of iPS Cells and ES Cells .................................................... 72 3.3.1 Genome ............................................................................................... 73 3.3.2 Transcriptome ..................................................................................... 73 3.3.3 Epigenome .......................................................................................... 74 3.3.4 Developmental Potential: Pluripotency .............................................. 75

3.4 Mechanism of Reprogramming ...................................................................... 76 3.4.1 Reprogramming Factors ..................................................................... 76

3.4.1.1 POU Domain, Class 5, Transcription Factor 1 (Pou5f1, Oct4) ...................................................................... 76

3.4.1.2 SRY-Box Containing Gene 2 (Sox2) ....................................77 3.4.1.3 Myelocytomatosis Oncogene (Myc, c-Myc) ........................77 3.4.1.4 Kruppel-Like Factor 4 (Klf4) .............................................. 78 3.4.1.5 Nanog Homeobox (Nanog) .................................................. 78 3.4.1.6 Lin-28 Homolog (Lin28) ...................................................... 78

3.4.2 Silencing of Integrated Retroviral Vectors in iPS Cells ..................... 79 3.4.3 Signal Networks .................................................................................. 81

3.4.3.1 Transcription Factor Networks ............................................ 81 3.4.3.2 Signal Transduction Pathway: Ground Level of

Self-Renewal ........................................................................ 82

In 1493, Spanish explorer Juan Ponce de León left Spain with Christopher Columbus on an epic quest for the mythical and biblical Fountain of Youth. He believed that drinking this legendary water would give him eternal life. To a biologist, a cellular “fountain of youth” would allow a cell or cell line to not only survive inde—nitely but also retain the plasticity of youth, the ability of a cell to differentiate into any cell type in the body. Scientists have been studying embryonic cells’ ability to do this for more than 50 years; however, what gives these cells this ability and how to create it in other cells have been elusive. While Ponce de León’s quest was ultimately fruitless, recent advancements in the —eld of stem cell biology have made the molecular quest for longevity and plasticity within reach.