Abstract below

Meryem B. Baghdadi

Institut Necker-Enfants Malades (INEM)

Stem cell niche regulation in homeostasis and disease

Abstract : Tissue turnover and regeneration are orchestrated by stem cells that both differentiate and self-renew. The intestinal epithelium constitutes an excellent model for studying stem cell biology due to its continuous renewal and remarkable ability to regenerate after acute and chronic injury. Mammalian intestinal stem cells (ISCs) are located in a pocket-like structure called the crypt and respond to signals within their microenvironment to maintain the balance of self-renewal, proliferation, and lineage commitment. It is thus essential to understand how stem cells integrate niche signals to maintain homeostasis. In addition to biochemical factors, the stem cell niche is also subjected to physical cues that might influence ISC behavior. However, how intestinal stem cells integrate the mechanical signals from their niche in vivo remains unclear. Stem cells sense and respond to mechanical cues via the integrated activation of different signaling pathways. This mechanotransduction process eventually leads to changes in cell shape, gene expression, and cell fate. PIEZO ion channels, which include PIEZO1 and PIEZO2, are an important group of mechanosensitive signaling receptors. These channels open in response to mechanical stimuli, allowing calcium to flow into the cell, activating downstream signaling pathways. PIEZO1 and 2 are highly expressed in mammalian intestinal epithelial cells, making PIEZO channels strong candidates for mechanotransduction of extrinsic signals in ISCs.