Introduction to stem cell regulation

Stem cells are cells that have the ability to self-renew and differentiate into various other cell types. The regulation of stem cells between these states is crucial in determining their behavior and ensuring they meet the patterning and morphogenetic needs of the embryo and mature tissue. This regulation is mainly influenced by the stem cell niche, which is the microenvironment surrounding a stem cell. Each tissue type has a unique stem cell niche and although the architecture of different niches may vary, there are common principles of regulation that apply to all.

Extracellular Regulation

• Physical mechanisms: Structural and adhesion factors within the extracellular matrix influence stem cell behavior. The cell density and cell-to-cell and cell-to-matrix adhesions within the niche can alter the mechanical forces that affect stem cell behavior.
• Chemical regulation: Surrounding cells secrete proteins that influence stem cell states and differentiation through endocrine, paracrine, or juxtacrine mechanisms. These signaling factors maintain stem cells in an uncommitted state, but once stem cells are positioned away from the niche, differentiation commences.

Intracellular Regulation

• Regulation by cytoplasmic determinants: At cytokinesis, the partitioning of cytoplasmic determinants influences cell fate. Asymmetric differentiating division occurs when factors determining cell fate are partitioned to one daughter cell, while symmetrical division occurs when these factors are shared evenly between daughter cells.
• Transcriptional regulation: A network of transcription factors regulates stem cell behavior by keeping them in a quiescent or proliferative state, and promoting the maturation of daughter cells towards a particular fate.
• Epigenetic regulation: Chromatin patterns influence gene expression related to stem cell behavior, and this occurs at the level of chromatin.

Conclusion

The specific intracellular mechanisms used by a stem cell are the downstream result of the extracellular stimuli in its niche, as well as the stem cell’s developmental history within the niche. Different stem cell niches have their own developmental origins and specific extracellular and intracellular mechanisms important for regulating stem cell behavior.