intestinal stem cell homeostasis

Definition

Target type: biologicalprocess

Any biological process involved in the maintenance of the steady-state number of intestinal stem cells within a population of cells. [GOC:nhn, PMID:22042863, PMID:22608824]

Intestinal stem cell homeostasis is a tightly regulated process that ensures the continuous renewal of the intestinal epithelium. This process relies on a population of intestinal stem cells (ISCs) located at the base of the crypts of Lieberkühn, which are invaginations in the intestinal lining. ISCs possess the remarkable ability to self-renew and differentiate into all the cell types that make up the intestinal epithelium, including absorptive enterocytes, mucus-secreting goblet cells, hormone-producing enteroendocrine cells, and Paneth cells.

Paneth cells, located at the crypt base, play a crucial role in maintaining ISC niche by secreting antimicrobial peptides and growth factors, which contribute to ISC survival and proliferation. The ISC niche also comprises other cellular components, including mesenchymal cells and immune cells, which provide structural support and regulate ISC behavior.

The Wnt signaling pathway is central to ISC self-renewal and proliferation. Wnt ligands secreted from Paneth cells activate the Wnt signaling pathway within ISCs, promoting their proliferation and preventing differentiation. The Notch signaling pathway, on the other hand, regulates ISC differentiation. Notch activation triggers ISCs to differentiate into specific cell types, such as enterocytes or goblet cells.

ISCs undergo asymmetric division, resulting in one daughter cell that retains stem cell properties and another that commits to differentiation. This ensures the maintenance of the ISC pool while continuously generating differentiated cells.

The balance between ISC proliferation and differentiation is tightly regulated by various factors, including growth factors, cytokines, and mechanical cues. For example, the growth factor epidermal growth factor (EGF) promotes ISC proliferation, while transforming growth factor-beta (TGF-β) inhibits ISC proliferation and promotes differentiation.

Disruptions in intestinal stem cell homeostasis can lead to various gastrointestinal diseases, including inflammatory bowel disease (IBD), colorectal cancer, and malabsorption syndromes. The understanding of ISC biology and the intricate mechanisms that govern ISC homeostasis provides a foundation for developing novel therapeutic strategies for these diseases.'
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Proteins (3)

Compounds (27)