These cells are known as transient amplifying cells and are formed through he differentiation of Huffs (Ditto & Coteries, 2005). This paper will seek to examine a specific protein within the HUFFS known as Rasa-related G botulism toxin substrate 1 recombinant protein (Arc 1). Through intrinsic expression, Race – a small GET protein is crucial for the maintenance and the proliferating Huffs. Through increasing evidence, scientists have accredited this to the negative regulation of c-NYC protein via appropriation.
The paper will discuss two experiments conducted that exhibit the function of Race . Through further analysis of the Race pathway, scientists see a potential to use he findings from this pathway in order to generate medication and curative therapy for growing epidemics. Introduction: Stem cells are characterized by their lack of specialization, self regeneration, and ability to produce a significant quantity of differentiated cells. These cells can be categorized into either embryonic stem cells or adult stem cells (Saccade, 2006).
While embryonic stem are specifically plenteous and arise from the inner walls of balloonists, adult stem cells can be further segregated into germ line stem cells and somatic stem cells. Both divisions within the dull stem cells may have properties of either plenipotentiary or omnipotence (Lie, L. & Xii, T. , 2005). The rate at which proliferation occurs and the maintenance of the adult stem cell’s identity is determines by the stem cell niche (Saccade, 2006). Purpose of a Stem Cell Niche: Somatic stem cells are organized in a special cellular organization known as a niche (Watt ; Hogan, 2000; Lie ; Xii, 2005).
Within a niche, stem cells are known to self-regenerate and infrequently divide (Ammo, 2009). The cells present in the micromanagement are constituents of a niche, fostering a lately and sheltering environment by allowing stem cells to maintain homeostasis between the tissues and also sequestering the stimuli of: differentiation, excessive proliferation and optimism, endangering the stem cell reservoir (Moore ; Limericks, 2006). The primary function of a stem cell niche is to maintain a balance between stem cell quiescence and activity (Moore ; Limericks, 2006).
Morphology of the Hair F-logical Niche: Within the mammalian skin, the presence of two distinct stem cell populations controls the maintenance of the epidermis and its associated trustees: the hair follicle stem cells (Huffs) and the intermolecular stem cells (Fiefs) (Moore ; Limericks, 2006). Huffs are located in the stem cell bulge, and are lined by the basal layer. They are present beneath sebaceous gland and in the crevice of a muscle know as the erector Pill, while the Fiefs are present in the base of the hair follicle (Appendix, Figure 1).
Another important feature of the hair follicle niche is the dermal papilla, located at the base of the hair follicle (Appendix, Figure 1). Composed of mechanical cells, the signals discharged by the dermal papillae cells maintain stem cell identity (Sprawling, A. Et al. , 2001). One protein that the dermal papilla expresses is the protein noggin; responsible for hair follicle growth through the repression of the protein Bump (Moore and Limericks, 2006).
Although not associated with hair growth directly, the dermal sheath layer, which surrounds exterior of the basal layer, contains progenitor cells that maintain and regenerate the dermal papilla, a key component for hair growth Dado ; Reynolds, 2001) Within the stem cell niche, the proximity of the stem cells to other constituents of the environment is essential in maintaining the identity of the stem cell reservoir (Ditto camp; Coteries, 2005). Overall, the niche is surrounded by a rich density of sensory nerve fibers and blood vessels, which replenish it with the delivery of essential nutrients (Fuchs, E..
Tumbler, T. ; Such, G.. 2004). The Race protein Race, Rasa-related CO botulism toxin substrate 1, is a member of the Rasa protein family and as such it is a signaling G protein; more specifically it is a small Stage – a hydroxyls enzyme. Race is intrinsically expressed within the Huffs present in the bulge of the hair follicle. Within mammals, when active, he Arc 1 protein is responsible for the management of a multitude of cellular processes, some of which include: controlling cell development and the activation of protein kingies (Moore et al, 2006).
However, within the HUFFS niche exclusively, Race is critically involved in the plutocratic regulation of epithelial differentiation and the control of stem cells departing from their niche. The Race protein is also responsible for maintaining the development of acting cytokines and the regulation of interring expression, two key factors essential for maintenance of stem cell identity, via downstream exultation. (Beneath S. Et al. , 2005). Signals Upstream and Downstream of Race protein Understanding the mechanism upstream of Race protein is essential in understanding the protein’s regulation and function in the hair follicle.
Many researchers have hypothesized that a specific niche environment would send out the stimuli to Race to augment its function in the maintenance of quiescent Huffs. (Ditto & Stairwells, 2005). Researchers have suggested that Tamil CT-lymphoma invasion and metastasis 1), a GET exchange factor, is perhaps responsible for the activation of Race , as it is a GET binding protein (Appendix, Figure 2). Through in vivo experimentation upon mice, it was observed that mice lacking the Tamil exchange factor exhibit an increasing De-sensitivity towards skin cancer formation. Ditto & Stairwells, 2005) This is in agreement with the speculation amidst researchers that skin tumors originate from stem cells. Researchers have inferred that the absence of Tamil would lead to a decrease in Race activation and thus the presence offer cells. (Ditto & Stairwells, 2005) Downstream of Race , its primary interaction is with the c-NYC protein; regulatory protein responsible for the transcription of specific genes which in-turn, are expressed through the production of proteins (Appendix, Figure 2).
Expressed intrinsically in Huffs, if c-NYC is over-expressed, it leads to an increase in terminal differentiation. Adversely affecting the stem cell reserve through its depletion (Moore and Limericks, 2006). Depletion of the stem cell reserve is accredited to the reduction of acting cytokines constituents and the expression Of interring – receptors that mediate between the cell and surrounding tissue. C-NYC is negatively regulated by Race in the sense that its repose is to disturb the adhesive interface between stem cells and their niches thus preventing stem cell differentiation.
The major components and processes involved in the c-NYC and Race pathway are: the activation of pop activated kinas 2 (PEAK), through means of phosphorescently, the inhibition of c-NYC and ultimately terminal differentiation of Huffs (Moore et al, 2006). Experiment 1: The Effects of Deleting Race protein Through the application of 40TH treatment upon the skin of knockout mice, the effect of deleting the Race protein and its loss of function was observed Beneath,Frye, Gloater & Watt, 2005). Through the deletion of Race protein, researchers Beneath et al. Observed the effects of the lack of this protein in mice, and noted severe conditions of hyperplasia and accredited it to the hyperventilation of transient cells and the differentiation of epidermal cells prematurely (Ditto & Stairwells, 2005). Some of the symptoms noted include: the development of cysts and excessive hair loss amidst the mice specimen (Appendix, Figure 3). This suggests that this small GET binding protein, Race if lost would prevent hair follicle stem cell renewal Ditto & Stairwells, 2005).
This finding further implies that Race, under standard conditions, is responsible for the maintenance of the HUFFS niche, through the suppression of the stimuli that allows the first transition to committed cell populations (Ditto & Stairwells, 2005). Beneath et al further concluded, that the skin thinning phenotype would be accredited to a delayed maturation of transient amplifying cells into terminal differentiated cells, due to a depleted stem cell reservoir. Ditto & Stairwells, 2005) As a control, in wild-type mice, through staining measures of the Race protein, a gig expression of Race was observed at the basal layer of the epidermis, particularly at the bulge and at the bulb of the hair follicle. (Beneath,Frye, Gloater & Watt, 2005). The high prevalence of Race in the bulge, the reservoir for Huffs, indicates that this protein is essential for the maintenance of stem cells.
Experiment 2: Race protein’s Negative Regulation of c-NYC via PEAK Physiotherapists Understanding the downstream mechanism of Race , helps one to understand the proteins that Race regulates in order for cell differentiation to take place. C-NYC is a transcription factor hat is known to be regulated by Race, through the phosphorescently of Peak, an enzyme. In vitro studies have shown that hyperventilation of transient cells and a depletion of HUFFS reserve, in the long-term, is correlated with an increase in c-NYC protein expression (Ditto ; Stairwells, 2005).
Through an elegant model, it was proposed that c-NYC activity is regulated through the activation of Race , which sends out the stimuli to suppress HUFFS depletion (Ditto ; Stairwells, 2005). However, other researchers fail to accept this model as cross connections between the Race protein, and other pathways ay play a larger role in the differentiation of Huffs. Conclusion: In conclusion, the Race protein is proposed to play a substantial role in the maintenance of the intermolecular epidermis in mice, which may be a reflection of all mammals.
Via experimentation, it was concluded that the Race protein is essential in the maintenance of Hair Follicle Stem Cell identity and its proliferation through this protein’s deletion. Furthermore, through intrinsic expression, it was further noted that within the hair follicle niche, it inhibits c-NYC through the phosphorescently of PEAK. Many scientists believe hat by better understanding the Race pathway, therapeutic remedies could be developed to intervene in the processes of wound healing, aging, hair loss and possibly cancer (Ditto & Stairwells, 2005).
Appendix: Figure 1 : The schematic diagram depicts the major constituents of the hair follicle niche. It depicts the relative positions and the spatial orientation of the cells that comprise the hair follicle. The Bulge Stem Cells are highlighted in red. The stem cells may either self-renew or differentiate to melancholy’s in the bulb of the hair follicle by leaving the stem cell niche. Figure 2: The schematic diagram depicts the different pathways that may affect the Race protein. One possible pathway would be once a stimuli passes through the membrane, it is affects Tamil a KEF mediated effecter, which then would stimulate the Race protein.
