Chapter 23 Essays A

  1. Generally speaking, explain skin. 

    1) Make up
    a.       It is made of several different cell types. To function as a barrier, the outer covering of the skin depends on a variety of supporting cells and structures. It needs mechanical support, provided by the ECM, mainly secreted by fibroblasts. It needs a blood supply to bringnutrients and oxygen and remove wastes and carbon dioxide, and this requires a network of blood vessels, lined with endothelial cells. 
  2. Generally speaking, explain skin. 

    1) Vessels
    a.       These vessels also provide access routes for cells of the immune system to defend against infection: macrophages and dendritic cells, to phagocytose invading pathogens and help activate lymphocytes, and lymphocytes themselves, to mediate more sophisticated adaptive immune system responses. 
  3. Generally speaking, explain skin. 

    1) Nerve fibers
    Nerve fibers are needed to convey sensory information from the tissue to the central nervous system, and to deliver signals in the opposite direction for glandular secretion and smooth muscle contraction
  4. What do complex mechanisms do?
    a.       They regulate the distribution of these structure and their distinctive patterns of growth and renewal. The regions of less specialized, more or less flat epithelium covering the body surface between the hair follicles and other appendages are called interfollicular epidermis. This has a simple organization, and it provides a good introduction to the way in which tissues of the adult body are continually renewed. 
  5. What do complex mechanisms do?
    regulate the distribution of these structure and their distinctive patterns of growth and renewal.

    The regions of less specialized, more or less flat epithelium covering the body surface between the hair follicles and other appendages are called interfollicular epidermis. This has a simple organization
  6. 1)      Explain the outermost cells of the granular layer.
    a.       They are reduced to flattened scales, or squames, filled with densely packed keratin. The plasma membrnaes of both the squames and the outer granular cells are reinforced on their cytoplasmic surface by a thin (12 nm), tough, cross-linked layer of proteins, including a cytoplasmic protein called involucrin. The squames themselves are normally so compressed and thin
  7. 1)      Explain how the epidermal cells differentiate.
    a.       While some basal cells are dividing, adding to the population in the basal layer, others are slipping out of the basal cell layer into the prickle cell layer, taking the first step on their outward journey. When they reach the granular layer, the cells start to lose their nucleus and cytoplasmic organelles, through a degradative mechanism that involves partial activation of the machinery of apoptosis; in this way, the cells are transformed into the keratinized squames of the keratinized layer. These finally flake off from the surface of the skin. 
  8. 1)      As the new keratinocyte in the basal layer is transformed into the squame in the outermost layers, what does it do? 
    a.       It steps through a succession of different states of gene expression, synthesizing a succession of different members of the keratin protein family, as well as other proteins 
  9. 1)      In the basal layer, what is required? 
    Cells that remain undifferentiated and carry on dividing, continually producing descendants that differentiate. There needs to be a self-renewing process. It must therefore contain some cells that generate a mixture of progeny, including daughters that remain undifferentiated like their parent, as well as daughters that differentiate. These are stem cells
  10. 1)      What are the two ways that 50% of stem cells remain as stem cells? 
    environmental and divisional asymmetry
  11. Environmental symmetry
    the division of a stem cell could generate two initially similar daughters whose fates would be governed by their subsequent environment or by some random process with an appropriate environmentally controlled probability; 50% of the population of daughters would remain as stem cells, but the two daughters of an individual stem cell in the population might often have the same fate.
  12. divisional asymmetry
    Divisional asymmetry: the stem cell division could be always strictly asymmetric, producing one daughter that inherits the stem-cell character and another that inherits factors that force it to embark on differentiation. There is a drawback with this—it means that the existing stem cells can never increase their numbers, and any loss of stem cells is irreparable, unless by recruitment of some other type of cell to become a stem cell. 
  13. 1)      Explain what happens if a patch of epidermis is destroyed? 
    a.       The surrounding epidermal cells repair the damage by migrating in and proliferating to cover the denuded area. In this process, a new self-renewing patch of epidermis is established, implying that additional stem cells have been generated to make up for the loss, which were produced by symmetric divisions in which one stem cell gives rise to two. 
  14. 1)      What does proliferative potential correlate with? 
    a.       It correlates with the expression of the Beta 1 subunit of integrin, which helps mediate adhesion to the basal lamina. Clusters of cells with high levels of this molecule are found in the basal layer of the intact human epidermis also, and they are thought to contain stem cells. 
  15. 1)      Explain experiments with bromodeoxyuridine (BrdU).
    a.       A pulse of BrdU is given to a young animal, in which the epidermis is growing rapidly, or to a mature animal following an injury that provokes rapid repair. One waits for many days or weeks before fixing the tissue and staining with an antibody that recognizes DNA in which BrdU has been incorporated. The BrdU is taken up by any cell that is in S phase of the division cycle at the time of the initial pulse. Because the Brd would be expected to be diluted by half at each subsequent cell division, any cells that remain strongly labeled at the time of fixation are assumed to have undergone few or no divisions since replicating their DNA at the time of the pulse.
  16. After experiments with BrdU, what can be seen?
    a.       Such label-retaining cells can be seen scattered among unlabeled or lightly labeled cells in the basal layer of the epidermis even after a period of several months, and large numbers are visible in hair follicles, in a region called the bulge. Ingenious labeling procedures indicate that the label-retaiing cells, int eh hair follicle at least, are in fact stem cells: when a new cycle of hair growth begins after an old hair has been shed, the label-retaining cells in the bulge at last divide and contribute the cells that go to form the regenerated hair follicle. 
  17. Aside from label-retaining cells, what is mixed with these cells?
    a.       Mixed with these cells there are others that divide more frequently—but only for a limited number of division cycles, after which they leave the basal layer and differentiate. These latter cells are called transit amplifying cells—transit because they are in transit from a stem-cell character to a differentiated character; and amplifying because the division cycles they go through have the effect of amplifying the number of differentiated progeny that result from a single stem-cell division. 
  18. 1)      What does the fact that transit amplifying cells are a common feature of stem cell systems mean? 
    a.       In most such systems there are few true stem cells and they are mixed with a much larger number of progeny cells that have only a limited capacity to divide.
  19. 1)      How is growth halted? 
    • a.       One way is by feedback signals that operate over much larger distances in the mature organism
    • b.      Another endows each founder cell with an internal program dictating that it shall divide a limited number of times and then stop so that way, short-range signals during development can define the size of large final structures. To continulalyl renew the adult tissue, founder cells are specified as stem cells, continue dividing indefinitely, and producing at each divison one daughter that remains as a stem cell and one that goes through a limited number of transit amplifying divisions and then stopping. 
  20. 1)      What was the use of BrdU?
    a.       BrdU was incorporated into the DNA of stem cells during the pulse period. Because they divide rarely, the label dilutes slowly by newly synthesized DNA.
  21. 1)      What are the benefits of transit amplifying divisions? 
    • a.       It means that the number of stem cells can be small and their division rate can be low, even when terminallyd fiferentiated cells have to be produced rpidly in large numbers. This reduces the cumulative burden of genetic damage, and mutations in cells that are not stem cells are discarded in the course of tissue renewal
    • A low stem-cell division rate in normal circumstances allows for dramatic increase when there is an urgent need in wound repair. The stem cells can then be roused to divide rapidly, and the additional division cycles can both amplify the stock of stem cells and increase steeply the production of cells committed to terminal differentiation
  22. 1)      Where does cell turnover have to be controlled? 
    • The rate of stem-cell division
    • the probability that a stem-cell daughter will remain a stem cell
    • the number of cell divisions of TACs
    • the timing of exit from the basal layer
    • the time that the cell then takes to complete its differentiation program and be sloughed from the surface
  23. 1)      With these control points, there are signals that regulate them. What are some of the influences? 
    a.       One is contact with the basal lamina, signaled via integrins in the plasma membrane of the cells. If cultured basal keratinocytes are held in suspension, instead of being allowed to settle and attach to the bottom of the culture dish, they all stop dividing and differentiate. To remain as an epidermal stem cell, it is apparently necessary to be attached to the basal lamina or the ECM. This requirement helps ensure that the size of the stem cell population does not increase without limit. If crowded out of their regular niche on the basal lamina, the cells lose their stem cell character. When this rule is broken, the result can be an ever-growing tumor. 
  24. 1)      What does Hedgeog signaling do? Wnt?
    • a.       It helps to guide the choice of differentiation pathway: a deficit of Hedgehog signaling leads to loss of sebaceous glands, while an excess can cause sebaceous glands to develop in regions where they would never normally form.
    • Similarly, loss of Wnt signaling leads to failure of hair follicle development, while excessive activation of this pathway cause extra hair follicles to form and grow excessively so that they give rise to tumors. 
  25. 1)      What does Notch signaling do? 
    a.       It seems to restrict the size of the stem cell population, inhibiting neighbors of stem cells from remaining as stem cells and causing them to become transit amplifying cells instead. And TGF-Beta has a key role in signaling to the dermis during the repair of skin wounds, promoting the formation of collagen-rich scar tissue. 
  26. 1)      Why are keratinocytes dynamic? 
    • a.       They change their appearance from one layer to the next.
    •                                                               i.      Those in the innermost layer, attached to an underlying basal lamina, are basal cells. They are the only ones that usually divide
    •                                                             ii.      Above basal cells are prickle cells with numerous desmosomes
    •                                                           iii.      Beyond the prickle cells lies the thin, darkly staining granular cell layer
Card Set
Chapter 23 Essays A