Lecture 6 - The stem cell niche Flashcards
Describe the potency of stem cells initially in the embryo?
Totipotent
What cells are produced from mesenchymal stem cells?
- bone cells (osteoblasts)
- cartilage cells (chondrocytes)
- fat cells (adipocytes)
What cells are produced from haematopoetic stem cells?
- blood stem cells
- red blood cells
- platelets
- white blood stem cells
What cells are produced from satellite stem cells?
muscle
What cells are produced from germ cells?
- oocytes
- sperm
What is the name given to the special environments where adult stem cells are found?
niches
Why do we need stem cells?
maintenance
How long do RBC live for?
4 months
How long do white blood cells live for?
> a year
How long do skin cells live for?
2-3 weeks
How long do colon cells live for?
4 days
How long do sperm cells live for?
3 days
How long do brain cells last?
can live for an entire lifetime
What process allows stem cell to carry out maintenance?
mitosis
How is stem cell division different from normal mitosis?
creates a daughter cell and keeps a stem cell
What is the advantage of stem cell division compared to normal mitosis?
maintains the stem cell population
What is the name of the stage by which the daughter cell, created through stem cell division, differentiates to create many cells?
transit amplifying stage
What is population asymmetry?
3 different types of division to ensure that division rates are in balance that keep the stem cell population constant
What are the 3 types of cell division which maintains population asymmetry?
- stem cell proliferates into 2 stem cells
- stem cell proliferates into 2 differentiated cells
- stem cell proliferates into one of each
What are the 3 main layers of the skin?
epidermis, dermis & subcutis
What can be found in skin?
- hair follicles
- sebaceous glands
- sweat glands
What is the epidermis made up of?
keratinocytes
What does the dermis contain?
fibroblasts & blood vessels
What stimulates keratinocyte proliferation?
signals from the dermis & basement membrane
What type of stem cells (that can proliferate) can be found in the stem cell niche that is the basal layer?
basal keratinocytes
What happens to the daughter cells (basal keratinocytes) when they proliferate?
pushed progressively to the skin surface where they die
What provides the skin with strength?
high levels of fibrous protein keratin
What happens to cells as they move towards the surface?
produce different keratin
Where are dead keratinocytes found?
on the outer layer of the skin
What separates & holds the dermis and epidermis together?
extracellular matrix
What signals come from the dermis that impacts differentiation?
Wnt
How does Wnt (from dermis) impact differentiation?
Wnt inhibits differentiation, which maintains stem cell population
How does Integrins maintain stem cell population?
Integrins hold cells to the basement membrane. This adhesion allows for the maintenance of stem cell population.
How do notch signals influence the maintenance of stem cell population?
Notch signals in maturing keratinocytes inhibit integrins. This stops adhesion between cells and the basement membrane. As a result, this causes a reduction in stem cell populations.
What is the protein that can inhibit Notch signal activity?
EGF (epidermal growth factor)
What is the stem cell niche located in the hair follicle?
the bulge
What is the purpose of the bulge found in the hair follicle?
Provide the cells that form the follicle
What can bulge cells contribute when skin is badly damaged?
bulge cells can also contribute to epidermis & sebaceous glands, which can aid in the replacement of damaged skin.
What occurs as a whole to stem cell niches after injury, when larger areas of restoration are needed?
different stem cell niches may be able to provide cells
What occurs in patients with Junctional epidermolysis bullosa (JEB)?
the adhesion between dermis and epidermis is impaired, due to mutation in adhesion genes - LAMB3
What can be used to replace skin in burn patients?
Skin epidermis (basal keratinocytes) that have been cultured
What can be used to reintroduce DNA into cells, when skin epidermis have been cultured from JEB patients?
inactivated viruses (viral vectors)
Why does our gut lining need to be continuously replenished?
Due to the harsh environment created due to our gut content
What are the different types of cells found in the small intestine?
- enterocyte
- goblet cells
- enteroendocrine cells
- paneth cells
- stem cells
- submucosal cells
What process are enterocyte cells involved in?
absorption
What is the function of goblet cells?
Secrete mucus
What is the function of enteroendocrine cells?
secrete peptide hormones
What is the function of Paneth cells?
secrete anti-microbial peptides
What is the function of submucosal cells?
help maintain the stem cells
Where are stem cells located?
base of the crypt
How many cells does each crypt create in a mouse?
12 cells per hour
How many cells is a crypt made up of?
250 cells
What hormone does slow-dividing stem cells express?
Bim1
What hormone does fast-dividing stem cells express?
Lgr5
What are Bim1 & Lgr5 markers for?
Stem cells
How do we know that Lgr5 positive cells are stem cells?
Lineage tracing allows us to determine the fate of a cell
What can be made that causes single cells to express a marker?
Transgenes
How can embryonic stem cells be grown?
they can be isolated from the epiblast & grown in cell culture
How is the embryonic stem cells kept in a pluripotent state?
They are kept in specially defined conditions, with BMP & LIF present
What occurs if BMP & LIF signals were removed from the embryonic stem cells?
this would lead to differentiation into different cell types - each cell type requiring a specific set of conditions.
What is the difference between human and mouse ES cells?
human - pluripotent & require FGF + activin
mouse - totipotent & require different treatment (BMP & LIF)
What are the assays (tests) for pluripotency?
Expression of epiblast markers (transcription factors):
- Nanog
- Oct4
- Sox2
- Klf4
How are chimeras made?
created when ES cells are mixed in with a normal embryo & the ES cells contribute to different tissues in the adult
What are teratomas?
benign tumours that contain differentiated tissues
What occurs if we activate epiblast marker expression in differentiated cells?
the cells dedifferentiate and become stem cells
What factors are used to convert differentiated cells into IPS cells (induced pluripotent stem cells)?
Yamanaka factors
What is the advantage of using Yamanaka factors to create IPS cells instead of ES cells?
Ethically less complex - ES cells can be quite difficult to obtain