幹細胞ニッチ

A stem cell niche is a tissue microenvironment where stem cells remain quiescent until stimulated to differentiate and replace dead or damaged cells. The niche maintains a balance between stem cell quiescence and differentiation, allowing stem cells to produce progenitors periodically. Stromal cells, Paneth cells, and keratinocytes constitute specific niches in mammalian tissues alongside adult stem cells.

Stem cells interact with surrounding matrix and cellular components through soluble factors or cell adhesion molecules. These cell-cell and cell-matrix interactions activate signaling pathways including Notch, Wnt, or BMP, which keep quiescent stem cells undifferentiated and maintain their high self-renewal capacity. Stromal cells also provide survival signals preventing apoptotic death.

In response to stimuli such as injury, specific cytokines stimulate gene expression changes in stem cells. The cells undergo asymmetric division and produce progenitors that further differentiate into tissue-specific cells and migrate to their site of action. This process enables tissue regeneration and repair.

Hematopoietic stem cells reside in the bone marrow amongst osteoblastic cells and stromal cells. Epithelial stem cells live in the bulge area of hair follicles interacting with keratinocytes. In the intestine, intestinal stem cells are found in the crypt region interspersed with Paneth cells, which induce them to produce transit-amplifying cells and replace the villus every 3 to 5 days.

Excessive accumulation of reactive oxygen species during aging or cancer disrupts niche functioning. Stem cells proliferate uncontrollably and eventually lose their regenerative capacity. This disruption compromises the niche's ability to maintain the balance between stem cell quiescence and differentiation, leading to tissue dysfunction.

Transit-amplifying cells are progenitors produced by stem cells through asymmetric division. These cells further differentiate into tissue-specific cells and migrate to their site of action. The niche allows stem cells to produce transit-amplifying cells periodically, enabling continuous replacement of the body's damaged or dead cells.

Neural stem cells in the adult nervous system are found within the hippocampus region and produce neuroblasts and mature neurons. The neighboring endothelial cells in the hippocampus form the stem cell niche of the nervous system. These endothelial cells provide essential signals that support neural stem cell maintenance and differentiation.