title: Ex uno plures: molecular designs for embryonic pluripotency.
abstract: Pluripotent cells in embryos are situated near the apex of the hierarchy of developmental potential. They are capable of generating all cell types of the mammalian body proper. Therefore, they are the exemplar of stem cells. In vivo, pluripotent cells exist transiently and become expended within a few days of their establishment. Yet, when explanted into artificial culture conditions, they can be indefinitely propagated in vitro as pluripotent stem cell lines. A host of transcription factors and regulatory genes are now known to underpin the pluripotent state. Nonetheless, how pluripotent cells are equipped with their vast multilineage differentiation potential remains elusive. Consensus holds that pluripotency transcription factors prevent differentiation by inhibiting the expression of differentiation genes. However, this does not explain the developmental potential of pluripotent cells. We have presented another emergent perspective, namely, that pluripotency factors function as lineage specifiers that enable pluripotent cells to differentiate into specific lineages, therefore endowing pluripotent cells with their multilineage potential. Here we provide a comprehensive overview of the developmental biology, transcription factors, and extrinsic signaling associated with pluripotent cells, and their accompanying subtypes, in vitro heterogeneity and chromatin states. Although much has been learned since the appreciation of mammalian pluripotency in the 1950s and the derivation of embryonic stem cell lines in 1981, we will specifically emphasize what currently remains unclear. However, the view that pluripotency factors capacitate differentiation, recently corroborated by experimental evidence, might perhaps address the long-standing question of how pluripotent cells are endowed with their multilineage differentiation potential.
authors.affiliation: Department of Developmental Biology and the Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University School of Medicine, Stanford, California; Genome Institute of Singapore, Stem Cell & Regenerative Biology Group, Agency for Science, Technology & Research, Singapore; and Department of Medicine and the Beth Israel Deaconess Medical Center, Division of Hematology/Oncology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Loh
authors.affiliation: Department of Developmental Biology and the Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University School of Medicine, Stanford, California; Genome Institute of Singapore, Stem Cell & Regenerative Biology Group, Agency for Science, Technology & Research, Singapore; and Department of Medicine and the Beth Israel Deaconess Medical Center, Division of Hematology/Oncology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Bing
authors.initials: B
authors.lastname: Lim
authors.affiliation: Department of Developmental Biology and the Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University School of Medicine, Stanford, California; Genome Institute of Singapore, Stem Cell & Regenerative Biology Group, Agency for Science, Technology & Research, Singapore; and Department of Medicine and the Beth Israel Deaconess Medical Center, Division of Hematology/Oncology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Lay Teng
authors.initials: LT
authors.lastname: Ang
mesh_terms: D000818:Animals; D047108:Embryonic Development; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D008322:Mammals / Q000196:embryology*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology*