title: Developmentally programmed induction of differentiation inhibiting activity and the control of stem cell populations.
abstract: Differentiation inhibiting activity/leukemia inhibitory factor (DIA/LIF) is a glycoprotein that controls differentiation of pluripotential stem cells. Alternative transcription generates both diffusible and matrix-associated forms of DIA/LIF. Transcriptional analysis using a sensitive ribonuclease protection assay revealed that the two messages are expressed independently, consistent with the proposition that the two forms of DIA/LIF have distinct biological roles. DIA/LIF expression was found to be activated early during differentiation of embryonic stem (ES) cells, providing a mechanism for feedback regulation of stem cell renewal. Expression of DIA/LIF by mesenchymal cells was shown to be controlled in a paracrine manner by polypeptide regulatory factors. Specific expression of the two forms of DIA/LIF was also demonstrated in the egg cylinder-stage mouse embryo. The combination of cell type-specific and signal-specific regulation enables very precise control over DIA/LIF expression and may represent an important component of the regulatory networks that govern stem cell proliferation and differentiation during mammalian development.
authors.affiliation: Department of Biochemistry, University of Oxford, UK.
authors.forename: P D
authors.initials: PD
authors.lastname: Rathjen
authors.forename: J
authors.initials: J
authors.lastname: Nichols
authors.forename: S
authors.initials: S
authors.lastname: Toth
authors.forename: D R
authors.initials: DR
authors.lastname: Edwards
authors.forename: J K
authors.initials: JK
authors.lastname: Heath
authors.forename: A G
authors.initials: AG
authors.lastname: Smith
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002846:Chromatography, Affinity; D004622:Embryo, Mammalian; D005246:Feedback; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D051379:Mice; D008815:Mice, Inbred Strains; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D012333:RNA, Messenger; D014212:Tretinoin; D012313:RNA