specialized tissues, stem cells and tissue renewal Flashcards
what are stem cells
unspecialized cells
capable of renewing themselves
can be induced to differentiate into tissue or organ specific cells with specialized functions
what organs do stem cells regularly divide to repair and replace worn-out or damaged tissues
gut, bone marrow, and skin
what organs do stem cells only divide under special conditions
pancreas, brain, and heart
characteristics of stem cells
not terminally differentiated
can divide without limit
able to renew themselves (preventing depletion of stem cells)
undergo slow division
totopotency
ability of a cell to give rise to all cells of an organism, including embryonic and extra-embryonic tissues (placenta)
e.g. zygote
pluripotency
ability of a cell to give rise to all cells of the embryo and subsequently adult tissues
e.g. embryonic stem cells
multipotency
ability of a cell to give rise to different cell types of a given lineage
e.g. adult stem cells
two theories of how stem cell population is maintained
asymmetric division
independent choice
asymmetric division
creates 2 cells, one with stem cell characteristics and another with the ability to differentiate (due to presence of determinate in cytosol in original stem cell)
first round of division: 50/50 split
independent choice
division makes 2 identical cells but the outcome is random and/or influenced by environment (not 50/50 split but depends on the needs of the cell)
first round of division: 50/50 split; or both stem cells; or both differentiated cells
e. g. if everything in cell/tissue is good –> independent choice allows for both daughter cells to become stem cells
e. g. if tissue is injured –> independent choice allows for both daughter cells to become differentiated
asymmetric division cannot explain
how existing stem cells rapidly increase their numbers
e.g. doesn’t explain injury situation
internal signals that influence differentiation of stem cells
gene expression
external signals that influence differentiation of stem cells
microenvironment
- chemicals secreted by neighboring cells
- physical contact with neighboring cells
- stem cell - stem cell interaction
- molecules in the microenvironment: extracellular matrix; growth factors; oxygen tension; ionic strength; pH; metabolites like ATP
founder stem cells
each organ/tissue has fixed number of founder stem cell populations programmed to have fixed number of divisions
founder stem cells divide and give rise to one daughter cell that remains a stem cell and a set of cells that have a set number of transit amplifying divisions
define the size of large final structures
transit amplifying cells
transit from a cell with stem cell characteristics to a differentiated cell
programmed to divide for a limited number of times
strategy for growth control
adult stem cells
are tissue specific
multipotent
serve as an internal repair system (divide without limit to replenish damaged cells)
need a specialized microenvironment where they can stay as a stem cell
epidermis
outer covering of skin
creates a water barrier
made of epithelial cells
continuously repaired and renewed every 30 days
dermis
second layer of skin
rich in collagen
provides toughness
hypodermis
deepest layer of skin
fatty subcutaneous layer
outer layer of dermis
inner layer of dermis
loose connective tissue
dense connective tissue
fibroblasts
secrete extracellular matrix providing mechanical support
blood vessels of skin are lined with
endothelial cells
blood vessels function to supply nutrients and oxygen and remove waste products
innate immune cells in skin
macrophages and dendritic cells provide defense against microbes and pathogens
lymphocytes in skin provide
adaptive immune response
cells found in epidermis
keratinocytes
melanocytes
dendritic cells (langerhans)
cells found in loose connective tissue of dermis
macrophages
fibroblasts
collagen fibers
lymphocytes
cells found in dense connective tissue of dermis
fibroblasts
collagen fibers
elastic fibers
epidermis is a _____ layer made of _____
stratified
keratinocytes
basal cell layer is attached to
basal lamina which separates epidermis from dermis
basal cells are only ____ cells in epidermis
dividing/stem
prickle cells
have numerous desmosomes that attach tufts of keratin filaments
granular cells
last layer of cells that are metabolically active
sealed together to form a waterproof barrier
granular cell layer forms boundary between
inner metabolically active strata and outer dead epidermis cells
squame cells
flattened dead cells densely packed with keratin but with no organelles
slough off
cell layer of epidermis from basal lamina outward
basal lamina –> basal cell layer –> prickle cell layer –> granular cell layer –> keratinized squames
what is responsible for cell differentiation during renewal of epidermis? (cells changing from one layer to the next)
change in gene expression
basal layer has stem cells that
divide to maintain the basal layer and also supply cells that move to other layers by undergoing change in gene expression
what triggers cell differentiation in stem cells of epidermis
loss of contact with basal lamina
mediated via integrin signaling
what protein assists with stem cell adhesion to basal lamina
Beta1 subunit of integrin
when cells loss contact with basal lamina –> integrin expression decreases
what factors govern renewal of epidermis
rate of stem cell division
probability that one of the daughter cells will remain a stem cell
rate of division of transit amplifying cells
timing of exit from basal layer and the time the cell takes to differentiate and be sloughed away from the surface
hair grow upwards from
dermal papilla
sebaceous glands secrete
oily liquid called sebum that nourishes developing hair follicle and hair itself
hair follicle undergoes cycle of
growth, regression, and reconstruction
where are stem cells found in hair follicle
bulge
overactivation of hedgehog pathway
epidermal cells continue to divide even after exit from basal layer
underactivation of hedgehog pathway
results in loss of sebaceous glands
e.g. baldness
overactivation of Wnt signaling pathway
causes extra hair follicles to develop (gives rise to tumors)
underactivation of Wnt signaling pathway
leads to failure of hair follicle development
e.g. baldness
notch signaling
restricts size of stem cell population
e.g. cell that develops delta protein becomes dominant and inhibits surrounding cells from developing delta protein and instead develops notch receptor –> lateral inhibition
TGFBeta pathway
plays a role in repair of skin wounds promoting formation of collagen rich scar tissue
specialized epithelium covers certain parts of the body:
nose, ears, and eyes
sensory cells present in the sensory epithelium act as _____ converting signals from the environment into an electrical form that can be interpreted by CNS
transducers
eyes have _____
ears have _____
nose has _____
photoreceptors
auditory hair cells
olfactory sensory neurons
apical end of sensory neurons
detects the external stimulus and converts it into a change in membrane potential
e.g. dendrite
basal end of sensory neurons
makes a synapse with neurons that relay the sensory information to specific sites in the brain
e.g. axon
olfactory neurons are replaced every
30 days
olfactory neuron’s equivalent to dendrites
modified cilia (6-8 per neuron)
olfactory neuronal axon transmits information to
olfactory bulb in brain
supporting cells among olfactory neurons
hold neurons in place and separate them from one another
olfactory system stem cell
basal cell
humans have ____ odorant receptor genes whereas dogs have _____
350
1000
olfactory receptors work via what receptor pathway
GPCR
each olfactory neuron expresses only one gene enabling the cell to respond to
only one class of odorant
what feature of odorant is recognized by olfactory receptor
structural
a single olfactory receptor can bind to
a single class of odorant molecules
activated olfactory receptor activates
an intracellular G-protein (Golf)
Golf alpha subunit activates
adenylate cyclase produces cAMP which opens ion channels resulting in influx of sodium and calcium
influx of positive ions on olfactory neuron
generates an action potential
axon of neuron from same gene _____ and synapse together at same point in olfactory bulb (same glomerulus)
converge
relay station in brain for olfactory sense
glomeruli in olfactory bulb
how many glomeruli/bulb in mouse brain
1800
neural stem cells residing among the _____ in the olfactory epithelium generate replacements for the lost neurons
basal cells
when olfactory basal stem cells lose contact with basal lamina, cells
divide and differentiate into olfactory neurons
regernation of olfactory receptor cells is one of the only few instances of ______ in the CNS
adult neurogenesis
where are stem cells found in the brain
ventricles of forebrain
hippocampus
these stem cells can divide and produce neurons and glial cells
stem cells in ventricles migrate
to the olfactory bulb where they differentiate into olfactory neurons
stem cells in hippocampus
involved in learning and memory
about 1400 fresh neurons are generated everyday
experimental evidence for neural stem cells
neurospheres in medium A: (clusters of stem cells from ventricles and fetal brain) can grow into more stem cells –> transferred to medium B: dissociate and culture as monolayer –> transferred to medium C: cells differentiate into neurons and/or glial cells
what factors activates quiescent stem cell proliferation (neurogenesis in brain )
- learning
- antidepressants (norepinephrine)
- electrical stimulation (deep brain stimulation and electroconvulsive shock)
what is unique about planaria (freshwater flatworm)
undergoes cycles of de-growth and growth repeated indefinitely without impairing survival or fertility
what percent of cells in planaria are stem cells (neoblasts)
20%
cell cannibalism
dead cells in planaria are phagocytosed and digested using all the nutrition
transformation is common in what kind of species
non-mammalian species
e.g. newt limb following amputation –> differentiated muscle cells in the stump reenter the cell cycle, de-differentiate, and become embryonic cells and proliferate to form a lib bud similar to the embryo
