Among the many cells in the human body, there is one cell that shows the unique charm of the living body. They are delicate and delicate, only a few tens of microns in size to store all the genetic information of the offspring; they live endlessly, and the stem cell population, which accounts for only 0.03% of the entire cell pool, is enough to differentiate into an entire lineage. They are spermatogonial stem cells.
What are spermatogonial stem cells?
Spermatogonial stem cells are the initiating cells for spermatogenesis. They are located on the inside of the basal membrane of the curved seminal ducts in the male testicles and are differentiated from primitive germ cells. Dutch scientist de Rooij DG has proposed that spermatogonial stem cells have a dual potential in terms of functional definition: first, they can maintain self-renewal to supplement the stem cell pool; second, they can produce entire sperm lineages through proliferation and differentiation, continuously providing males with mature sperm.
Why are spermatogonial stem cells called "golden seeds"?
Why are small sperm stem cells called the "golden seeds" of male reproduction? This also starts with the process of sperm production. Back in the 1960s, scientists such as Rosen-Runge, Clermont and Huckins discovered some patterns of spermatogenesis in male mammals. Across the entire spermacretic lineage, spermatogenesis begins with a single type A seminal cell (A s). First, type A seminal cells are divided into pairs (A pr) by one and then into a chain of cells (A al) connected by intercellular bridges. In rodents, these larger chain clones differentiate into A1 seminal spermatoceles, which then produce A2, A3, A4, intermediate, and B seminal seminal cells through continuous mitosis, followed by primary spermblasts entering meiosis, producing secondary spermblasts and round sperm cells. Finally, the sperm cells undergo morphological changes, and mature sperm is produced. In a wave of perseminal spermatogenesis, these cells at different stages of differentiation are filled with segments of the seminal tubules. Spermatocytes, on the other hand, exist at the very top of the entire spermatogenesis lineage, a single type A seminal cell. Therefore, the quantity and quality of spermatogonial stem cells are directly related to the health and stability of the entire germ cell lineage.
Who decides the fate of the "Golden Seed"?
So, as the "leader" of the entire sperm production process, how do spermatogonial stem cells dominate the overall situation? From the definition of spermatogon stem cells, we can know that it can either produce cells exactly like itself through self-renewal, replenish them to the stem cell pool to maintain its own number of stability, or initiate division and spermatogenesis. Therefore, spermatogonial stem cells are particularly important for the choice of self-renewal and differentiation.
Figure 1 The fate of spermatogonial stem cells
According to the performance of stem cells in the process of self-renewal, they can be divided into four states: the vast majority of stem cells are in a resting state in the body, a small number of cells enter the cell proliferation cycle, and a stem cell and a progenitor cell are produced through asymmetric division, thereby maintaining the stability of the stem cell pool in vivo. However, in some special cases, stem cells also achieve amplification in numbers by symmetric division. When the body is damaged or stimulated, stem cells may also produce two progenitor cells into differentiation to meet the needs of local tissue proliferation repair, resulting in a decrease in the total number of stem cells. So, what are the regulators that determine the fate of stem cells? Studies have shown that stem cells renew or differentiate themselves largely depending on the "signals" they receive. These "signals" come from both the cell itself and the "microenvironment" in which it resides.
For self-expressed cytokines, it is mainly regulated by the methylation modification of genes, the methylation and acetylation modification of histones, and microRNAs. These signaling molecules have a complex regulatory network that together precisely regulate the self-renewal and differentiation of stem cells. In addition to the cell's own regulatory system, the influencing factors in the "microenvironment" are also very important. Spermatophiles in vivo are in a "microenvironment" composed of support cells, interstitial cells and peri-tube muscle cells, which can secrete various growth factors to regulate the biological behavior of spermatomic stem cells, such as glial-derived neurotrophic factor (GDNF) can effectively promote cell self-renewal, colony stimulating factor 1 (CSF1) can promote cell proliferation, and the fibroblast growth factor (FGF) family also plays an important role in the proliferation and differentiation of spermatogonial stem cells.
Fig. 2 Determinants of spermatogonial stem cell fate
Application of spermatogonial stem cell culture in human assisted reproductive technology
In recent years, with the development of in vitro fertilization-embryo transfer technology, many male infertility patients can also produce their own offspring. For adult men, frozen stored sperm became the primary method of preserving fertility in chemotherapy patients.
However, for some pediatric malignancies and disease patients who need stem cell transplant treatment, the long-term culture and transplantation of sperm stem cells in vitro has become the only way for them to retain fertility without being able to preserve the sperm they produce.
Figure 3 Application of spermatogonial stem cells in human assisted reproductive technology
Therefore, we have never stopped exploring how to establish conditions that are more conducive to the maintenance of spermatogonial stem cells. It is believed that in the near future, human beings can continue countless healthy lives from generation to generation by mastering the fate of stem cells.
(The author is an experimentalist at Nanjing Medical University)