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Rendiconti Lincei

, Volume 16, Issue 2, pp 83–97 | Cite as

Mechanisms and factors in embryonic stem cell self-renewal

  • Ian Chambers
Article

Abstract

Embryonic stem (ES) cells are attracting renewed attention because their capacity to differentiate into cellular derivatives of all three primary germ layers suggests that they could be a source of cells for therapeutic alleviation of disease. This differentiative capacity, termed pluripotency, can be restrained during ES cell culturein vitro with the cells exhibiting an apparently unlimited capacity for symmetrical self-renewing divisions. A thorough understanding of self-renewal is essential if ES cells are to be fully exploited for therapeutic ends. Intrinsic self-renewal determinants include the homeodomain proteins Oct4 and Nanog. Increased Nanog expression alleviates the requirement for BMP and gp130 receptor stimulation and allows factor-independent ES cell self-renewal. Fusions between Nanog and GFP indicate that Nanog is localised to the cell nucleus consistent with a role as a transcriptional regulator. Mapping of the major transcription initiation site of Nanog paves the way towards identification of the factor(s) that direct Nanog gene expression and thus determine the pluripotent state.

Key words

Pluripotency Teratocarcinoma Nanog Oct4 STAT3 

Fattori e meccanismi che regolano i processi di self-renewal delle cellule embrionali staminali

Riassunto

Nell’ultimo decennio le cellule staminali embrionali (ES) hanno destato un crescente interesse in virtù della loro capacità di generare derivati cellulari differenziati dei tre foglietti germinali primari, prospettando quindi un loro utilizzo terapeutico in ambito biomedico. Il loro potenziale differenziativo intrinseco, indicato comunemente con il terminepluripotenza, può essere mantenuto durante l’espansione delle cellule ESin vitro, dove viene evidenziata un’apparente illimitata capacità di autorinnovamento cellulare (self-renewal) tramite processi di divisione cellulare simmetrica. Tuttavia, al fine di poter sfruttare appieno le potenzialità delle cellule ES per scopi terapeutici è fondamentale giungere ad una completa e profonda comprensione dei meccanismi e delle molecole che regolano i processi di self-renewal. Tra le varie molecole implicate in tali processi regolativi, Oct4 e Nanog, fattori di trascrizione della famiglia di geni homeobox, ricoprono un ruolo fondamentale. Infatti, la sovraespressione di Nanog è in grado di ridurre la dipendenza dai segnali mediati dall’attivazione dei recettori del BMP (Bone Morphogenetic Protein) e LIF (Leukemia Inhibitor Factor), permettendo l’espansione delle cellule ES in assenza di tali fattori solubili nel medium di coltura. Studi di localizzazione subcellulare condotti utilizzando proteine di fusione con la GFP (Green Fluorescent Protein) hanno evidenziato la localizzazione nucleare di Nanog, in accordo con il suo ruolo di regolatore trascrizionale. La caratterizzazione delle sequenze regolatorie contenute nel promotore di Nanog rappresenta quindi un nodo cruciale verso l’individuazione dei fattori che ne modulano l’espressione e regolano la pluripotenza delle cellule ES.

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Copyright information

© Springer 2005

Authors and Affiliations

  • Ian Chambers
    • 1
  1. 1.MRC Centre Development in Stem Cell Biology Institute for Stem Cell ResearchUniversity of Edinburgh King’s BuildingsEdinburghScozia

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