Developing stem cells: how are they driven by their microenvironment?

The development and function of stem cells in the organism are affected by the microenvironment, which is called the stem-cell niche. The stem cell gland niche is not a single structure but a dynamic microenvironment that includes surrounding cells, molecular signals, and stromal components that all work together to regulate stem cell fate. During embryonic development, glandular factors regulate the gene expression of embryonic stem cells, promoting cell proliferation or differentiation to promote fetal development. Therefore, the importance of this process is self-evident.

Stem cells are housed in specific anatomical locations, a location whose nature is understood by mediating their involvement in tissue generation, maintenance and repair.

In mature individuals, stem cell glands maintain the quiescent state of adult stem cells, but in the event of tissue damage, the surrounding microenvironment actively signals stem cells to self-renew or differentiate to form new tissue. The properties of stem cells are regulated by multiple factors, including cell-to-cell interactions between stem cells, interactions between stem cells and surrounding differentiated cells, and interactions between stem cells and adhesion molecules.

In addition, the composition of the extracellular matrix, oxygen concentration, various growth factors and cytokines, etc. will affect the behavior of stem cells. Interactions between stem cells and their microenvironment can induce each other to develop and jointly maintain function. In this area of ​​research, scientists hope to be able to recreate the conditions of stem cell glands in vitro and further advance the development of regenerative medicine.

For regenerative therapies, it is critical to control cell proliferation and differentiation in culture flasks so that sufficient numbers of specific cell types can be generated prior to treatment.

Ordinary embryonic stem cells are usually grown in a medium containing fibroblast growth factor-2 and fetal calf serum, and placed on a cell substrate that supports the pluripotent properties of stem cells. However, even these conditions cannot completely simulate the glandular environment in vivo. Adult stem cells remain undifferentiated throughout life, but often undergo an "aging" process when cultured in vitro, which includes changes in cell morphology and a decrease in proliferation capacity.

The specific location of the stem cell gland site is not enough to define the gland site, it must have the dual dimensions of anatomy and function.

By performing serial live imaging studies in mice, scientists were able to explore the structure of stem cell glandular niches and obtain the fate of individual stem cells and their progeny over time. In the densification of the intestine, two distinct populations of stem cells have been found: "marginal stem cells" located in the upper part of the gland and "central stem cells" located at the base of the densification. The proliferation potential of these two groups of stem cells is unequal and related to the location of the cells. This shows that the structure of the glandular site and its effect on stem cells is so critical.

Stem cell glands have a two-component structure. This biological understanding, through mathematical modeling, can be used to minimize the probability of mutation, and this process essentially provides an important basis for the maintenance of stem cells. In such a dynamic system, stem cells interact and influence each other with the microenvironment to form a balance, which is crucial to maintaining tissue health.

Glandular site size represents an evolutionary trade-off between cancer and aging, which is a question worth pondering.

In academia, the concept of stem cell gland sites was first widely used in vertebrates, but the first characterization study of it during the reproductive development of Drosophila has provided us with precious information. In the Drosophila ovary, the stem cell gland contains key components of the ovarian genome, further deepening our understanding of the gland. Such research not only gives us a more comprehensive understanding of the role of stem cells, but may also lay an important foundation for future regenerative medicine.

Faced with such scientific discoveries, we can’t help but think: How will future technology help us better utilize the potential of stem cells?

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