Pluripotency Factors on Their Lineage Move

Figure 1

Signalling pathways regulating pluripotency in mESCs. A schematic representation of the main extrinsic pathways (LIF, BMP, and WNT) regulating pluripotency in mESCs. Upon LIF binding to its receptor, Gp130 phosphorylates JAK, which in turn phosphorylates STAT3. Phosphorylated STAT3 operates as a transcription factor which sustains the pluripotency state in mESCs and further inhibits endodermal and mesodermal differentiation. LIF further inhibits GSK3 via PI3K. GSK3 stabilises the self-renewal state by reducing the ubiquitin dependent degradation of β-catenin. WNT proteins bind the Frizzled receptor which in turn forms a complex with LRP5/6 protein and signal downstream via Dsh and β-catenin. β-catenin accumulates in the cytoplasm and nucleus resulting in STAT3 transcription. STAT3 is activated through JAK phosphorylation. Upon BMP4-receptor complex formation, BMP RI phosphorylates SMAD1 and SMAD5 which then interacts with SMAD4 resulting in Id gene transcription and maintenance of the pluripotency state. Image modified after Hao [7]. Dsh: dishevelled, ERK: extracellular receptor kinase, Id: inhibitor of differentiation, JAK: Janus kinase, and mESCs: murine embryoid stem cells. LIF: leukaemia inhibitory factor, MAPK: mitogen-activated protein kinase, Oct3/4: octamer binding transcription factor 3/4, PI3K: phosphatidylinositide 3′-kinase, SMAD1/4/5: mothers against decapentaplegic homolog 1/4/5, STAT3: signal transducers and activators of transcription 3, RI: receptor type I, RII: receptor type II, and WNT: wingless-related MMTV integration site family.