Lecture 6&7 Flashcards
Specialized architecture of auditory hair cells in organ of Corti
- ear drum hits the membrane, membrane vibrates and this affects the fluid
Cell turnover
Some cells are specialized and therefore cannot regenerate if they are damaged (ie. auditory hair cells/photoreceptors
Architecture of Ear and Generation of Action Potential
sound causes vibration of basilar membrane, which then causes the fluid to move the tectorial membrane
- sound waves cause stereocilia atop hair cells to tilt
- tilt towards tallest: open of ion channels, which creates a nerve impulse
- sound waves are then converted to nerve impulses
Mammals and hair cells
- cannot regenerate when they are lost
- the loss can be due to diesase, toxins, extreme noise
- other vertebrates can replicate these cells
Stereocillia Dynamics at the Molecular Level
- stereocilia are filled and supported by actin
- actin continually polarized –> treadmilling
Human photoreceptor as a permanent cell type
- another type of permanent cell
- photoreceptors convert light waves into nerve impulses
- use a pulse chase experiment
Extracellular Turnover: bone
extracellular matrix that forms bone is continually digested by osteoclasts and deposited by osteoblasts
- osteoclasts move around, destroying the bone
- osteoblast secrete bone…eventually will be trapped and turns into osteocytes
Stem Cell
- not terminally differentiated
- can divide without limit
- daughters can remain a stem cell or differentiate
- cell turnover can be dependent on these cells or not
Cell Renewal
- cell renewal can occur from division of differentiated cells as well (not just step cells)
Control of the fates of stem cell daughters
- Division Asymmetry
Divisional Asymmetry
- one daughter receives factors promoting “stemness”, and the other receives factors promoting differentiation
drawback: if stem cells are lost, their original numbers cannot be restored
Environmental Asymmetry
- cell division is symmetric
- fate determined by the environment
- if stem cells are lost, then their numbers can be increased by having btoh daughters of division enter environment promoting stemness
Slow division of stem cells
Protects cells from:
- mutations associated with cell division
- Telomere depletion associated with cell division
- there is a committed transit amplifying cell
Skin stem cells and their progeny
- stem cell reside in basal layer, they require attachment. Basal lamina provides a niche for stem cells
- after detachment: differentiation through a linear sequence of cell types
- without renewal: skin lost for a month
Blood Stem Cells and their Progeny: Haematopoiesis
- blood stem cells differentiate into various populations creating a branched pathway to a final differentiation
Common Lymphoid Progenitor
Developed thymus – T cell
B cell
Dendritic Cell
NK cell
Common Myeloid progenitor
- dendritic cell, neutrophil, monocyte –> macrophage, osteoclast
- eosinophil
- basophil, mast cell
- I) megakaryocyte –> platelets
II) erythrocyte
Blood stem cells and their progeny reside in bow marrow
A mouse was x-irradiated, which halted blood cell production…without treatment it would die
So you inject bone marrow cells from a healthy donor
- the mouse survives; the injected stem cells colonize its hemopoietic tissues and generate a steady supply of new blood cells
Identifying blood stem cells and their progeny
homogenize mouse bone marrow to release single cells
expose cells to fluorescent antibodies recognizing specific cell surface molecules
Isolate labelled cells by FACS
basically separate stem cell by charge
garbage is collected in the flask
- a cell has a fluorescent antibody, it is the stem cell so we will give it a negative charge; if not the charge is positive (can see this through laser)
Maintenance of Blood Stem Cells
- mainted through i/a with stromal cells in bone marrow
- stroma cells provide a niche for the blood stem cells
- if we want a stem cell to stay a stem cell, it MUST be attached to the stromal cell
- Kit binding
- stem cell is attached to stromal cell through Kit…transit amplifying detaches and cell will differentation or die or can stay maintained
Stem Cell and Progeny Regulation
- for the supply of correct numbers of differentiated cells
Stem cell to committed progenitor:
1. frequency of stem-cell division
2. probability of stem-cell death
3. probability that stem-cell daughter will become a (II)committed progenitor cell of the given type
4. Division cycle time of committed progenitor ccell
5. Probability of progenitor cell death
(III)
6. Number of committed progenitor cell divisions before terminal differentiation
IV)
7. Lifetime of differentiated cells
Stem cells and tissue renewal can affect how we age and can treat diseases and disabilities
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Medical Uses for Stem cells
- can use blood stem cells to treat leukemia
problems of immune rejection - careful tissue matching and immunosuppressive drugs
- if cancer arises from a mutation in one of the progenitor populations, then the patient’s own stem cells can be sued after sporting
- if cancer arises, use electronic sorting technique to collect stem cells again, and destroy all the other cells
Can cells of a different tissue be used to make stem cells for treatment?
occurs naturally during limb regeneration in newts
- muscle cells de-defferentiate, become mono-nucleated and start dividing
- a bud similar to the embryonic limb bud is formed from the cells
- their progeny form all of the cellt ypes needed to re-grow the limb