specialized tissues, stem cells and tissue renewal Flashcards by Colt Moller

what are stem cells

unspecialized cells

capable of renewing themselves

can be induced to differentiate into tissue or organ specific cells with specialized functions

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what organs do stem cells regularly divide to repair and replace worn-out or damaged tissues

gut, bone marrow, and skin

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what organs do stem cells only divide under special conditions

pancreas, brain, and heart

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characteristics of stem cells

not terminally differentiated

can divide without limit

able to renew themselves (preventing depletion of stem cells)

undergo slow division

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totopotency

ability of a cell to give rise to all cells of an organism, including embryonic and extra-embryonic tissues (placenta)

e.g. zygote

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pluripotency

ability of a cell to give rise to all cells of the embryo and subsequently adult tissues

e.g. embryonic stem cells

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multipotency

ability of a cell to give rise to different cell types of a given lineage

e.g. adult stem cells

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two theories of how stem cell population is maintained

asymmetric division

independent choice

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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

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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

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asymmetric division cannot explain

how existing stem cells rapidly increase their numbers

e.g. doesn’t explain injury situation

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internal signals that influence differentiation of stem cells

gene expression

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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

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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

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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

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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

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epidermis

outer covering of skin

creates a water barrier

made of epithelial cells

continuously repaired and renewed every 30 days

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dermis

second layer of skin

rich in collagen

provides toughness

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hypodermis

deepest layer of skin

fatty subcutaneous layer

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outer layer of dermis

inner layer of dermis

loose connective tissue

dense connective tissue

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fibroblasts

secrete extracellular matrix providing mechanical support

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blood vessels of skin are lined with

endothelial cells

blood vessels function to supply nutrients and oxygen and remove waste products

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innate immune cells in skin

macrophages and dendritic cells provide defense against microbes and pathogens

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lymphocytes in skin provide

adaptive immune response

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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