Tissue Homeostasis Flashcards
What are stem cells and why are they needed in adults?
- Cells that can renew tissues that slowly loose cells
- slow dividing
- imortal
- protection against accumulation of mutations
What are examples of why stem cells are needed?
- Blood cells: adult RBC die every 100 days and dont have a nucleus so can’t proliferate
- Gut cells: epithelium (lining of the gut) renewed
- Skin surface cells: renewed often and dont have a nucleus
How is asymetrical division generated?
- Environment (neighbouring cells/ECM/GF)
- inside cell’s localised compartment
What were the effects of radiation on the haematopoetic system?
Stem cells discovered after WW2 hiroshima bomb. Increased radiation= death but could be saved by bone marrow transplant
What did Till and McCulloh discover and how?
Found that transplanted bone marrow could save radiated mice.
Radiating bone marrow= death
Transplanting radiated bone marrow= death
Showed that mice spleen came from 1 bone marrow cell bc found colonies all had the same mutation from the radiated bone cell.
Do plants have stem cells?
Yes? they have apical meristems that seem to give rise to different cells.
What stem cell therapies are there?
Bone marrow transplants after irradiation are used in leukemia therapy
What is the niche for in Drosophilia GSC cells?
germline stem cells
Niche=stem cell environment that provides stuff needed to maintain stem cells
Cap cells are the niche. They provide signals that turn Bam off (keep it as stem cells)
What phenotype do BAM mutants have?
Loss of function mutants have too many germ cells. Means that Bam on triggers GSC’s to differentiate
How do spectrosomes create asymetrical division?
The cell that inherets the spectrosome when it divides remains the GSC. GSC anchored to niche by adheren. Spectrosome made of spectrin (binds actin)
GSC’s are linked to cap cells (their niche) by spectrosomes because creates orientated division of the cells away from the cap cells, therefore the new cells have Bam ON opposed to the ones that stay near the cap cells where Bam is OFF
What is mamillian hair follicle an example of?
Mamillian stem cells that undergo asymetric division. The cells that remain anchored are the self renewable ones.
What cell types compose the gut epithelium?
Enterocytes: absorb nutrients (villi)
Goblet cells: secrete mucus (villi)
Enteroendocrine cell: secretes hormones (villi)
Paneth cell: mediates microbial immunity (base of crypt)
CBC cells: express Lgr5 aka stem cell (base of crypt)
crypt base columnar= CBC
How were gut stem cells (Lgr5+) discovered?
First GFP was added to the promoter region of Lgr5. Then the promoter was engineered to express CreET2, which is only active when tamoxifen. When CreET2 is on it turns on LacZ (blue) in the Lgr5 cells. So cells that express Lgr5 would be blue/green and their descendents were blue. The blue/green ones always stayed in the crypt proving CBC were stem cells
How was it proven that Paneth cells were the niche for CBC?
CBC makes gut organoids in vitro, but only really grow with paneth cells. Paneth cells can be replaced by Wnt3, prooving Paneth cells are the niche for CBC.
Do CBC divide asymetrically or symetrically? How was this determined?
They divide symetrically. Each CBC was tagged with a fluoresence protein, and after a while each crypt was one color- prooves they divide symetrically. Follows a neutral drift model
Why? In a limited space its likely that one of the 5-7 cbc dominated eventually over the rest of them- which fits mathmatically. There is another posibility that the crypt is all one stem cell but this isnt likely
What organs regenerate well?
Gut, skin, haemopoetic system
What organs regenerate slowly?
Muscle, liver
What organs do not regenerate well?
Lens, brain, heart
How are TA cells involved in regeneration?
TA= transient amplifying
They are a back up. When Lgr5+ cells are radiated they die (bc no lacz label) but still Lgr5+ are found in crypt and villus (w/o lacZ). Implies TA cells were turned into stem cells.
Regarding gut regeneration
What did the assisted regeneration experiement show?
Healthy gut organoids could be transplanted and save a dying mouse. Shows that Wnt3 essential for growing organoid and also that they have healing properties.
What are the different layers of the epidermis?
- Cornified
- Suprabasal
- Basal
- Dermis
How does the epidermis regenerate cells?
Stem cells are in the basal layer. They proliferate and give rise to suprabasal cells. Suprabasal cells make their way up and lay down a protein matrix, then ennucleate themselves and die. Doing this creates a barrier against pathogens or stressors
How do scientists grow skin?
Scientists can propigate holoclones (stem cells) which can be applied to burn victims and give them new skin
Epidermal cells give rise to 3 colonies in vitro: holoclone, merclone, and pariclone of which only holoclone lived ‘forever’
What are satellite cells?
Long thin multinucleated cells that are Muscle stem cells, used to regenerate muscles and are located on the edge of muscle fibres
