The gastrointestinal tract stem cell niche

Abstract

The gastrointestinal epithelium is unique in that cell proliferation, differentiation, and apoptosis occur in an orderly fashion along the crypt-villus axis. The intestinal crypt is mainly a proliferative compartment, is monoclonal and is maintained by stem cells. The villus represents the differentiated compartment, and is polyclonal as it receives cells from multiple crypts. In the small intestine, cell migration begins near the base of the crypt, and cells migrate from here emerging onto the villi. The basal crypt cells at position 5 are candidate stem cells. As the function of stem cells is to maintain the integrity of the intestinal epithelium, it must self-renew, proliferate, and differentiate within a protective niche. This niche is made up of proliferating and differentiating epithelial cells and surrounding mesenchymal cells. These mesenchymal cells promote the epithelial- mesenchymal crosstalk required to maintain the niche. A stochastic model of cell division has been proposed to explain how a single common ancestral stem cell exists from which all stem cells in a niche are descended. Our group has argued that these crypts then clonally expand by crypt fission, forming two daughters' crypts, and that this is the mechanism by which mutated stem cells or even cancer stem cell clones expand in the colon and in the entire gastrointestinal tract. Until recently, the differentiation potential of stem cells into adult tissues has been thought to be limited to cell lineages in the organ from which they were derived. Bone marrow cells are rare among adult stem cells regarding their abundance and role in the continuous, lifelong, physiological replenishment of circulating cells. In human and mice experiments, we have shown that bone marrow can contribute to the regeneration of intestinal myofibroblasts and thereby after epithelium following damage, through replacing the cells, which maintain the stem cells niche. Little is known about the markers characterizing the stem and transit amplifying populations of the gastrointestinal tract, although musashi-1 and hairy and enhancer of split homolog-1 have been proposed. As the mammalian gastrointestinal tract develops from the embryonic gut, it is made up of an endodermally-derived epithelium surrounded by cells of mesoderm origin. Cell signaling between these two tissue layers plays a critical role in coordinating patterning and organogenesis of the gut and its derivatives. Many lines of evidence have revealed that Wnt signaling is the most dominant force in controlling cell proliferation, differentiation, and apoptosis along the crypt-villus axis. We have found Wnt messenger RNAs expression in intestinal subepithelial myofibroblasts and frizzled messenger RNAs expression in both myofibroblasts and crypt epithelium. Moreover, there are many other factors, for example, bone morphogenetic protein, homeobox, forkhead, hedgehog, homeodomain, and platelet-derived growth factor that are also important to stem cell signaling in the gastrointestinal tract.

Role of LRF/Pokemon in lineage fate decisions

“…A stem cell niche is defined as an environment in which stem cells are not only hosted but also supported in their self-renewal 41 and are instructed to differentiate into specific cell lineages. In mammals, stem cell niches have been described in many different organs: HSC niches in the bone marrow, 42 the epithelial stem cell niche in the skin, 43 the intestinal stem cell niche, 44 neural stem cell niches in the brain, 45 and the germ-line stem cell niche, which was identified in mouse testis. 46 HSCs and their bone marrow niche together make up one of the most studied microenvironment systems.…”

Biomimmetic surfaces effectively inhibiting coagulation process dedicated for cardiovascular devices

“…In mammals, stem cell niches have been identified in different tissues over the past several years, including bone marrow, brain tissues, hair follicles, the intestines, and teeth [21][22][23][24][25][26]. Theoretically, a stem cell niche is composed of the stem cells themselves along with stromal support cells, extra cellular matrix proteins, blood vessels and neural inputs.…”

Intestinal stem cells and stem cell-based therapy for intestinal diseases

“…One such tissue is the intestinal tissue. In anatomical terms, the intestinal tissue consists of two main parts; the small intestine and the colon (Simons and Clevers 2011;Yen and Wright 2006). Internally, this intestinal tissue is lined with epithelium.…”