The role of regulation of gene expression is becoming more and more complex and integrated in the structural phenotype of the cells and the organism as a whole. This regulatory control is most evident and indeed most variable in the differentiation of the stem cells in to its various progeny. Stem cells are the first cells that develop in the embryo. These stem cells later on differentiate themselves, creating mnore complex progenies, and this division and maturity of the progeny then leads to the culmination of the final cells, which are entirely different from the original cells.
Due to the natural property of the stem cells to differentiate themselves into particular cells, the search is on to understand how stem cells change into one particular type of cell and not the other. (Morrison, Shah and Anderson, 1997, pp. 287) The question here is how stem cells are able to know which phenotype to convert into and are there any mechanisms that help them to their final destination. It is this property of diversity that they are named the “mother of all cells” (Morrison, Shah and Anderson, 1997, pp. 288).
Stem cell research has mainly developed itself due to the researches carried out on the hemopoietic cell system and therefore contributes to the bulk of knowledge. Current researches while working towards identifying the contributing genes and patterns of cell maturation, are pointing towards the same thing; that each stem cell has a genetic predisposition towards a specific line of phenotypes. And that these stem cells are under the strict control of the various external and internal regulatory systems of the body cells.
As to what accounts for the stem cells to choose one phenotype over another is still a matter of debate. Many think that since the regulatory mechanisms are important controls of the maturation of the cells, may be triggering of one particular regulation mechanism leads to the formation of a particular phenotype. This is a very crude attempt of explanation for a mechanism that is perhaps the most complex of all the cell mechanisms. Still, it may be the starting point towards the understanding of the mysteries of the stem cells.
The three main functions of the stem cells are to self maintain and retaining the ability to self maintain. This is in order to provide a continuous supply of cells for future proliferation and differentiation of cells. The cells are also able to provide a multitude of differentiated cells from a single progeny. However, these progeny cells are mainly of one line only, although variations may exist. An example is the presence of the mast cells that change themselves according to the specific cell need of their surroundings.
Pluripotency however, is a feature that is of variable presence in the different stem cells. Again, the cells that have shown high pluripotency include the heamopoeitic stem cells and it is for this reason these have been extensively studied in stem cell researches. (Potten and Loeffler, 1990, pp. 1013) Among these the CD series of cells is able to provide the body with all the blood cells when needed, again signifying some sort of control in the stem cells to differentiate into one particular lineage of cells. (Steidl et al, 2002, pp. 2038) A simplified schematic diagram of the hematopoietic hierarchy.
The hematopoietic stem cell (HSC) sits at the top of the hierarchy. Upon activation, the HSC is capable of differentiating into clonal progenitors that can expand exponentially as well as continue the process of differentiating. Hematopoietic cells are broadly divided into “lymphoid” and “myeloid cells”. Lymphoid cells include T cells, B cells, natural killer cells, and dendritic cells. Myeloid cells include red blood cells, platelets, monocytes/macrophages, and granulocytes (as well as other cell type such as eosinophils, mast cells, and basophils).
A more detailed description of the initial stages of HSC differentiation is provided in Figure 2. (Nemeth and Bodline, 2007) While this regenerative and duplicative capacity of the stem cells is remarkable, such cells are extremely active and sensitive to stimuli, and therefore require extensive regulatory mechanisms. It is therefore, a very complicating task to multiply these cells in the laboratories. The differentiation potential to a specific phenotype in the laboratory is only possible if the regulatory and the stimulating mechanisms are understood.
The variations in the exposure to the different stimuli can lead to differentiation of the cells in to a specific phenotype. Of the many regulatory mechanisms, some of the well known regulatory entities include the LAG-2, GLP-1, EGF and TGF-?. Again even the slightest evolution of these stem cells may lead to limitations of the stem cell pluripotency. Of the many features that distinguish the HSCs and the committed progenitors, the two most characteristic are “the multipotency versus the oligopotency and life-long self renewal versus the absence of self renewal” (Terskikh et al, 2003, pp.
98) The more the cells are non committed the more influence of the factors such as the CBP, ATF4, general transcription factor II-I, as well as the signal transduction pathways has been seen. (Terskikh et al, 2003, pp. 98) The transcription factor family has been shown to be of immense importance in the proper development of the vertebrates. (Park et al, 2002, pp. 495) Yet little is still known about the various genes that regulate the human population of stem cells as most of the information is derived from rat and mouse models.
In most of these cases, the findings are now being correlated and genes are being compared in both models in order to analyze the synchronicity between them. (Sperger et al, 2003, pp. 13351) The implication of the emergence of human germ cell tumors is now being attributed to the human teratocarcinomas, a feature seen in young males, as well as seminomas, a feature absent in the mice models. (Sperger et al, 2003, 13352) What is important to note is the specificity of these particular stem cells to differentiate only into seminomas and cancer of the testicular tissue and not some other kind of cancerous condition.
In the teratocarcinoma case, there has been seen the presence of transcription factor POUF51 only thought to occur in the embryonic cells. Other similar kinds of factors include the DNMT3B, TERF1, FOXD3 and multiple unigene clusters to name a few. (Sperger et al, 2003,pp. 1352) The presence of fetal and embryonic proteins in the adult cells has removed the illusion that these types of cells are present in only developing fetuses, and signify that this may be indication of the cells from the regulatory controls and reversion to their differentiation potential.