39.3:
Stem Cell Niche
The stem cell niche is a tissue microenvironment where the stem cells remain in a quiescent state until stimulated to differentiate and replace dead or damaged cells.
Stromal cells in the bone marrow, Paneth cells in the intestine, and keratinocytes of skin epithelium alongside the adult stem cells constitute specific niches in mammalian tissues.
The stem cells interact with their surrounding matrix and cellular components via soluble factors or cell adhesion molecules.
Such cell-cell and cell-matrix interactions activate one or more signaling pathways, including Notch, Wnt, or BMP, which keep quiescent stem cells undifferentiated and maintain their high self-renewal capacity.
In response to a stimulus, such as an injury, specific cytokines stimulate gene expression changes in the stem cells. The cells undergo asymmetric division and produce progenitors that further differentiate into tissue-specific cells and migrate to their site of action.
Excessive accumulation of reactive oxygen species during aging or cancer disrupts niche functioning. The stem cells proliferate uncontrollably and eventually lose their regenerative capacity.
39.3:
Stem Cell Niche
The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to the stem cells preventing their apoptotic death. This way, the niche allows stem cells to produce progenitors or transit-amplifying cells (TA cells) periodically and replace the body’s damaged or dead cells. Thus, the niche maintains a balance between stem cell quiescence and differentiation.
Adult tissues, including the bone marrow, skin, intestine, or brain, harbor stem cells inside specific niches. For example, hematopoietic stem cells (HSCs) reside amongst osteoblastic cells, stromal cells, and reticulocytes that form the bone marrow niche. The epithelial stem cells of the skin live in the bulge area of the hair follicles. These stem cells interact closely with keratinocytes and help regenerate the hair follicles. The neural stem cells of the adult nervous system are found within the hippocampus region that produces neuroblasts and mature neurons. The neighboring endothelial cells in the hippocampus form the stem cell niche of the nervous system. In the intestine, the intestinal stem cells or ISCs are found in the crypt region interspersed with the Paneth cells. Paneth cells constitute the intestinal stem cell niche and induce the ISCs to produce TA cells and replace the villus every 3 to 5 days.
Suggested Reading
- Moore, K. A., & Lemischka, I. R. (2006). Stem cells and their niches. Science, 311(5769), 1880-1885.
- Ferraro, F., Celso, C. L., & Scadden, D. (2010). Adult stem cells and their niches. The Cell Biology of Stem Cells, 155-168.