Self-renewal of teratocarcinoma and embryonic stem cells.
Pluripotent stem cells derived from preimplantation embryos, primordial germ cells or teratocarcinomas are currently unique in undergoing prolonged symmetrical self-renewal in culture. For mouse embryonic stem (ES) cells, self-renewal is dependent on signals from the cytokine leukaemia inhibitory factor (LIF) and from either serum or bone morphogenetic proteins (BMPs). In addition to the extrinsic regulation of gene expression, intrinsic transcriptional determinants are also required for maintenance of the undifferentiated state. These include Oct4, a member of the POU family of homeodomain proteins and a second recently identified homeodomain protein, Nanog. When overexpressed, Nanog allows ES cells to self-renew in the absence of the otherwise obligatory LIF and BMP signals. Although Nanog can act independent of the LIF signal, a contribution of both pathways provides maximal self-renewal efficiency. Nanog function also requires Oct4. Here, we review recent progress in ES cell self-renewal, relate this to the biology of teratocarcinomas and offer testable hypotheses to expose the mechanics of ES cell self-renewal.
Chambers
Ian
I
MRC Centre Development in Stem Cell Biology, Institute for Stem Cell Research, University of Edinburgh, King's Buildings, West Mains Rd., EH9 3JQ, Scotland, UK. ichambers@ed.ac.uk
Smith
Austin
A
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D045744:Cell Line, Tumor / Q000166:cytology / Q000187:drug effects; D002999:Clone Cells / Q000166:cytology / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D004622:Embryo, Mammalian / Q000166:cytology*; D054278:Embryonal Carcinoma Stem Cells; D006133:Growth Substances / Q000494:pharmacology / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000187:drug effects; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects; D018121:Receptors, Cytokine / Q000502:physiology; D017978:Receptors, Growth Factor / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D018243:Teratocarcinoma / Q000473:pathology*; D013736:Testicular Neoplasms / Q000473:pathology; D014157:Transcription Factors / Q000494:pharmacology / Q000502:physiology
D016207:Cytokines; D004268:DNA-Binding Proteins; D006133:Growth Substances; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D018121:Receptors, Cytokine; D017978:Receptors, Growth Factor; D014157:Transcription Factors