Wnt

The Wnt signalling pathway is a highly conserved molecular pathway that plays critical roles in regulating self-renewal and differentiation in various types of stem cells and operates through a complex cascade of signalling events. When Wnt ligands bind to receptors (Frizzled and LRP), signalling is initiated, ultimately leading to the stabilization and nuclear translocation of β-catenin. Nuclear β-catenin acts as a transcriptional co-activator, interacting with TCF/LEF transcription factors to regulate the expression of target genes that influence self-renewal, differentiation, and tissue homeostasis. Wnt signalling is critical for maintaining the pluripotency and self-renewal of ESCs. It regulates the expression of the core pluripotency factors Oct4, Nanog, and Sox2. Activation of the Wnt pathway acts to stabilize these factors preventing ESCs from differentiating prematurely. However, appropriate levels of Wnt signalling are necessary, as excessive activation can lead to differentiation. Like ESCs, the Wnt pathway plays a key role in iPSC generation and maintenance. Controlled activation of Wnt signalling enhances reprogramming efficiency and supports the pluripotent state of iPSCs. Activation of Wnt signalling pathways, often with small molecules like CHIR99021 or GSK3 inhibitors, can increase the reprogramming efficiency of somatic cells into iPSCs. This is partly because Wnt signalling promotes the epithelial-to-mesenchymal transition (EMT), an important step in the early stages of reprogramming. Moreover, Wnt signalling can activate key pluripotency-associated genes, such as Oct4, Nanog, and Sox2, which are essential for maintaining the pluripotent state. This activation contributes to the acquisition of pluripotency during iPSC generation. Conversely, inhibiting Wnt signalling can promote differentiation and lineage commitment in iPSCs. The Wnt pathway is also involved in regulating adult stem cells in various tissues. In some cases, Wnt signalling can promote self-renewal and maintenance. For example, in the intestinal epithelium, Wnt signalling is important for the proliferation and self-renewal of intestinal stem cells (ISCs). Cells in the intestinal crypts, where ISCs are located, produce Wnt ligands which act activate Wnt signalling pathways in ISCs. Wnt signalling forms a gradient along the crypt-villus axis of the intestine with levels of Wnt signalling at the base of the crypts promoting ISC self-renewal, whilst lower levels of Wnt signalling as cells migrate up the villus guiding differentiation into various intestinal cell types, including absorptive enterocytes and secretory cells (goblet, Paneth, and enteroendocrine cells). Similarly, in hair follicles, it regulates the behaviour of hair follicle stem cells, ensuring proper hair growth and cycling. However, the role of Wnt signalling in adult stem cells is context dependent. In some tissues, such as the hematopoietic system, excessive Wnt signalling can lead to stem cell exhaustion and myeloid malignancies. The balance of Wnt signalling is therefore often essential for maintaining proper stem cell function. Dysregulation of the Wnt pathway is often associated with cancer, including CSCs, which may be responsible for tumour initiation, progression, and recurrence in some cancers. In some cancer types, hyperactive Wnt signalling can drive CSC self-renewal and therefore tumour growth. For example, colorectal cancer often features mutations in Wnt pathway components, leading to uncontrolled proliferation of CSCs. We offer a wide product catalogue of research tools for studying the Wnt signalling pathway, including beta Catenin antibodies, HDAC3 antibodies, HDAC6 antibodies, beta Catenin ELISA Kits, and DKK1 ELISA Kits. Explore our full Wnt signalling pathway product range below and discover more, for less. Alternatively, you can explore our Cytoplasmic, Secreted, and HDACs product ranges.