Lecture 28: Specialized Tissues, Stem cells, and Tissue removal Flashcards
Characteristics of Stem cells:
- Not terminally differentiated
- Can divide without limit
- Undergo slow division
- When divide gives rise 1 cll with stem cell characteristics and the other with the ability to be differentiated
Are stem cells tissue specific
yes (e.g. epidermal stem cells, intestinal stem cells etc.)
- Maintenance of Stem Cells
- Steady pool of stem cell popluation, preceily 50% of daughter cells must remain as stem cells
- How is this accomplished?
- Steady pool of stem cell popluation, preceily 50% of daughter cells must remain as stem cells
- Asymmetric Division:
- Creates 2 cells, one with stem cell characteristics and another with the ability to differentiate
- Drawbacks:
- Cannot explain how existing stem cells increase their numbers
- Independent Choice:
- Division makes 2 identical cells but the outcome is stochastic and/or influenced by environment
- Advantages:
- More flexible
- explains the sharp increase in stem cell numbers when needed for repair
- Explains how environment may influence batches of cells and does not have to 50:50 for every division
- Advantages:
- Division makes 2 identical cells but the outcome is stochastic and/or influenced by environment
Example of how Stem cells selectively retain orginal DNA
- BrdU label is taken up by cells in S phase of cell cycle
- the label remains in stem cells for a long time
- could be due to slow rate of division or asymmetirc segregation of their DNA
- Asymmetiric segregation
- After division one of the daughter cells gets all the original DNA strands form all the chromosomes
- This daughter cell will retain the stem cell characteristics (with original strand of DNA preserved in and remains preserved from generation to generation)
- Second cell gets the newly synthesized strand
- (this maintence of the original DNA is a way for the stem cells to avoid genetic errors)
- Asymmetiric segregation
Immortal Strand Hypothesis
Asymetric divsion leads to the tagged DNA (immortal) being moved together throughout cell divisions this means the stem cell is able to keep original DNA
Architecture of Skin
- Epidermis
- Forms the outer covering of skin
- Creates a water barrier
- Made of epithelial cells
- Continuously repaired and renewed
- Dermis
- Second layer
- rich in collagen
- provides toughness
- Hypodermis
- Fatty subcutaneous layer
Extracellular matrix is secreted by ____ and provides mechanical support
Fibroblasts
Blood vessels lined with _____ supply nutrients/oxygen and remove waste products from skin
Endothelial cells
____ and ____ provide skin defense against microbes and pathogens while ____ provide adaptive immunity
Macrophages, dendritic cells, lymphocytes
epidermis is a stratified layer made of _______
keratinocytes (have keratin intermediate filaments)
____ cell layer attaches to the basal lamina
basal cell layer
hat is the only dividing cells in the epidermis
cells of the basal cell layer
Multilayered Structure of Epidermis
- Basal cell layer
- Attached to basal lamina
- Are only dividing cells in epidermis (stem cell layer)
- Prickle cell layer
- desmosomes that attach tufts of keratin filaments
- Granular cell layer
- sealed together to form a waterproff barrier
- fomrs a boundary between inner metabolically active strata and outer dead epidermis cells
- Squam layer
- Outmost layer
- flattended dead cells densely packed with keratin but no organelles
- Explain renewal of epidermis
- Basal cell are dividing cells
- in order to maintain layers above they divide and move into those layers
- When they reach a given layer they change expression and phenotype to match the layers
- as they move up they have partial degradation
- loss of nucleus and organells
- (note basal layer to shedding/surface presentaiton is one month)
- (note that it is the disconnection from the basal lamina that triggers differentiation)
Hair Follicle
- Hair grows upward from dermal papilla
- sebaceous glands secrete oily liquid called Sebum
- undergoes cycle of growth, regression, and reconstruction
- Stem cells present in a Bulge
- hlep in reconstruction and vives rise to hair follicle and interfollicular epidermis
Prolierative potential of stem cells in basal layer directly coorelates with expression of
- Beta 1 subunit of integrin (helps mediate adhesion to the basal lamina)
- (this means that clusters of cells with high levels of integrin are found in or near basal lamina and in bulge of hair follicle)
Transit Amplifying Cells
- A committed Daughter cell (from a stem cell) that undergoes some rounds of cell prolieration (a set number) but then stops dividing, terminally differentiates, and eventually is discarded and replaced.
- (think of them as twinners: characteristics of both a stem cell and a differentiated cell)
Factors Governing Renewal of Epidermis
- Rate of stem cell division
- Probability that one of the daughter cells will remain a stem cell
- Rate of division of the transit ampliying cells
- Timing of exit from basal layer and the time the cell takes to differentiate and be sloughed away from surface
Regulation of Epidermis Renewal
- Most important: Contact with basal lamina
- Mediated via integrin signaling (Beta 1)
- once contact is lost stem cell characteristics are abolished and cell differentiates
- Mediated via integrin signaling (Beta 1)
Signaling pathways in Epidermis Renewal
-
Hedgehog
- Overactivation of Hedgehog pathway makes cell continue to divide even after exit from basal layer.
- Deficit hedgehog signal leads to loss of sebaceous glands
- Overactivation of Hedgehog pathway makes cell continue to divide even after exit from basal layer.
-
Wnt signaling
-
up-regulation
- causes extra hair follicles ot develop (gives rise to tumors)
- Loss of signal
- leads to failure of hair follicle development
-
up-regulation
-
Notch
- Restricts size of stem cell population
- Results in lateral inhibition
- causes neighbors of stem cells to beocme transit amplifying cells
-
TGFß
- Key role in repair of skin wounds by promoting formation of collagen rich scar tissue
