Molecular Bases of Pluripotency

Publisher Summary This chapter focuses on the influence of the IL6 family of cytokines on ES cell pluripotency and self-renewal, extrinsic determinants of pluripotency, intrinsic determinants (i.e., transcription factors) of pluripotency, and epigenetic configuration of pluripotent cells in an attempt to define the molecular basis underlying pluripotency. Early mammalian embryogenesis is characterized by a gradual restriction in the developmental potential of the cells that constitute the embryo. The inner cells, termed inner cell mass (ICM), give rise to all cell lineages of the embryo proper, but cannot contribute to the trophoectoderm, and thus are considered pluripotent. Once isolated and cultured in vitro under permissive conditions, the ICM may be propagated as an embryonic stem (ES) cell line. These cells are the in vitro substitutes for embryos in the search for the genetic switches and molecular mechanisms required to ensure pluripotency. Mutations affecting the ability of ES cells to self-renew or differentiate and contribute to distinct cell lineages provide the necessary tools to unravel the molecular network underlying pluripotency. The therapeutic potential of induced pluripotent cells was tested in a sickle cell anemia mouse model. Induced pluripotent cells have also been derived from human fetal, neonatal, and adult fibroblasts by ectopic expression of the same four-factor cocktail that yielded mouse iPS. But genetic manipulation of cells also brings inevitable drawbacks; ectopic expression of c-Myc causes tumorigenicity, and random insertion of the viral sequences within the genome may produce unwanted mutagenesis events.