Regulation of embryonic stem cell self-renewal and pluripotency by leukaemia inhibitory factor

Hiroyuki Hirai, Peter Karian, Nobuaki Kikyo

Research output: Contribution to journalReview articlepeer-review

109 Scopus citations

Abstract

LIF (leukaemia inhibitory factor) is a key cytokine formaintaining self-renewal and pluripotency of mESCs (mouse embryonic stem cells). Upon binding to the LIF receptor, LIF activates three major intracellular signalling pathways: the JAK (Janus kinase)/STAT3 (signal transducer and activator of transcription 3), PI3K (phosphoinositide 3-kinase)/AKT and SHP2 [SH2 (Src homology 2) domain-containing tyrosine phosphatase 2]/MAPK (mitogen-activated protein kinase) pathways. These pathways converge to orchestrate the gene expression pattern specific to mESCs. Among the many signalling events downstream of the LIF receptor, activation and DNA binding of the transcription factor STAT3 plays a central role in transducing LIF's functions. The fundamental role of LIF for pluripotency was highlighted further by the discovery that LIF accelerates the conversion of epiblast-derived stem cells into a more fully pluripotent state. In the present review, we provide an overview of the three major LIF signalling pathways, the molecules that interact with STAT3 and the current interpretations of the roles of LIF in pluripotency.

Original languageEnglish (US)
Pages (from-to)11-23
Number of pages13
JournalBiochemical Journal
Volume438
Issue number1
DOIs
StatePublished - Aug 15 2011

Keywords

  • Cell differentiation
  • Embryonic stem cell (ESC)
  • Kinase inhibitor
  • Leukaemia inhibitory factor (LIF)
  • Protein phosphorylation
  • Signal transducer and activator of transcription 3 (STAT3)

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