Ananya Ghosal, MAKAUT, WB
Tissue Stem Cell has the ability to regenerate the function of host cell resulting in transplantation. At the time of regeneration, donor stem cells remain unknown. In quantitative clonal fate studies, a large population of donor spermatogonia stays in host testes, a small amount continues to regenerate for a long period and due to cell death and differentiation rest are lost. However, there is an increased repopulation efficiency of infertile hosts that restore fertility through transiently suppressing differentiation. From this, we get many applications from restoring fertility to conserving biological diversity through spermatogonial transplantation.
How can we restore fertility in mice?
Brinster developed the transplantation method, where a single cell suspension of donor testes is injected into the lumen of the mice, in which elimination of germ cells is done by the treatment with a cytotoxic reagent or genetic mutations. After setting down, translocation of donor spermatogonia occurs through Sertoli cells into the basal membrane in which spermatogonia (SSCs and amplifying progenitors) reside. After 2-3 months donor cell restores homeostatic sperm production, enhances the stages of spermatogenesis. The reconstituted spermatogonia reside in the basal compartment which is called the gap between the tight junction between Sertoli cells and basement membrane, where meiotic cells are the spermatocytes and haploid cells are called spermatids. In homeostasis, the glial cell line belongs to the GDNF family receptor alpha-1 (GFRα1), comprising of a self-renewing pool that results in differentiation- primed. Whereas neurogenin3 can rarely self-renew but differentiate into Kit+.
The transplantable SSC (spermatogonial stem cell) depends on the resultant colonies established over 2-3 months. B quantitative analysis of colon dynamics by applying a strategy of significant enhancement or repopulation efficiency by remodeling the post-transplantation fate of donor SSCs. In order to give rise to isolated cells or shorter syncytia, GFRα1+ cells migrate actively over the basement membrane by processing incomplete cell division forming syncytial length and syncytial fragmentation. GFRα1+ cells maintaining the numbers by interchanging between Aal, As and Apr, give rise to GFRα1– cells, resulting in highly variable fate.
Homeostatic spermatogenesis is quantitively predicted by a minimal model where GFRα1+ cells undergo multiple division, differentiation stochastically with defined probabilities of syncytial fragmentation. The resulting homeostatic, SSC colonies (groups of the spermatogonial stem cell) are unable to live long, which takes place if SSCs are renewed through invariant asymmetric division. Whereas, highly divergent where some expand and persist in SSC clones which contribute to long term self-renewal but others are lost by chance differentiation. Restoration of host fertility is done by WIN treatment on transplantation. The effect of WIN treatment has been evaluated on overall repopulation efficiency in the next generation and the host fertility with the use of UBI-EGFP mice showing ubiquitous GFP expression as a donor, observing a large increase long term repopulating colony in Win-treated hosts.
In WIN treated host, testes transplantation of an unfractionated testicular cell suspension lead to reconstitution of robust spermatogenesis in most of the seminiferous tubules. Resulting in 5-12 WIN-treated host donor-cell derived offspring with the mating of normal female mice. However, the offspring produced by WIN treated host was normal in growth and fertility. From here we conclude that the next generation individuals and sperm quality are not affected when the mice are treated with WIN or differentiating cells which recruited artificially and contribute long term repopulation of spermatogenesis and self-renewing pool.
Challenges
To simplify the assumption that SSC function, the transplantation takes place in a broadly homogenous environment. This experiment has a high predictive capacity which emphasizes the existence of the stochastic principle of SSC fate behavior. The modeling analysis captures the donor cell differentiation whereas separate net differentiation and reverse transition rate are not captured, which improves the strategies to increase the repopulation efficiency in transplantation in the emptied niche microenvironment, divergent fates, and donor spermatogonia exhibiting stochastic or stereotypic fate behavior to enable a definitive subpopulation to repopulate with an increase in probability.
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Reference
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