Lecture 9: Adult stem cells Flashcards
How often do cells turnover?
Vary massively! There must be cells within these tissue that contribute to repair
tissue specific stem cells:
- called ‘adult’ or tissue-specific stem cells
- can also be derived from foetal tissue
- build & repair tissue
- difficult to isolate & maintain in vitro
to repair tissue, stem cells have to:
- supply large numbers of DIFFERENTIATED cells
- BUT protect themselves from accumulating mutations
- AND stop themselves raging
- Adult stem cells have no telomerase
- -therefore telomeres will shorten until cells senesce
Telomeres:
- ends of linear chromosomes
- Repetitive DNA sequences (TTAGGG)
- Specialised proteins
- form a ‘capped’ end structure
DNA replication is
..bidirectional.
- Polymerase moves 5’ to 3’
- requires a labile primer
- each round of DNA replication leaves 50-200bp DNA unreplicated at the 3’ end
Generic Adult stem cell model:
Quiescent stem cell –Damage Physiological Stress–> Transit stem cell –Cell cycle entry –> Active Stem cell [back to beginning or] –> Progenitors -= expand
How are adult stem cells protected from mutations whilst still being able to repair tissue
by only dividing a few times and letting the progenitor expand
quiescent stem cells divide ____
asymmetrically to give progenitors, progenitors expand
Conventional ASC model: IMPLICATIONS
- cells flow through in unidirectional manner
- differentiation becomes restricted, through ORDERED, IRREVERSIBLE fate decisions i.e the stem cells are multipotent
why doesnt the generic model apply to all adult stem cell systems?
1) Not all Adult Stem cells are multipotent
2) Not all adult stem cells are quiescent
3) Flow through hierarchy is not always unidirectional
Not all adult stem cells are multipotent :
Some examples of UNIPOTENT set cells: Epidermal basal cells only make keratinocytes
Not all adult stem cells are quiescent:
e. g. intestinal crypt
- stem cells are continuously dividing
- give rise to more differentiated cells
- which then lead to transit amplifying cells
Each different tissue is likely to have evolved _____ strategy(s) to maintain the tissue normally & during repair
SLIGHTLY DIFFERENTLY
The fastest self-renewal tissue in a mammal:
Small Intestinal Crypt - Villus Unit
- Continous proliferation from base
- Crypt Base Columnar (CBC) cells are the long term stem cells
- CBCs divide to compete for niche space= those at base most likely to survive
Crypt Base Columnar (CBC’s) give rise to :
Enterocytes, Goblet cells, Paneth, Enteroendocrine cells.
-BUT there is another stem cell population = +4 LRC’s
Small Intestinal Crypt-Villus Unit CBCs r responsible for:
day-to-day regeneration.
- +4 LRC can revert to Lgr5+ stem cell, therefore NO ‘professional’ G0 stem cells exist
mammary gland: MaSC = multipoint give rise to:
- UNIPOTENT Myo-SC
- BIPOTENT Lum-SC
MasC are
SLOW cycling or G0
- MaSC are SLOW cycling or G0 –
[Normally - low hormonally drive tissue turnover.
Puberty = increase in ductal morphogenesis]
May be interconversion between Ductal and alveolar progenitors
Skeletal muscle: what are the stem cells?
- satellite cell
- Contribute minimally to myofibre maintenance.
- Damage – cells re-enter cell cycle- and under go either:
- Symmetric divisions to remake Stem cell pool
- Asymmetric divisions : myogenesis.
- satellite cells are the professional G0 stem cells BUT unipotent cf blood
‘NICHE’ in ecology:
Role and position a species has in its environment
“NICHE” in stem cell biology
a local tissue microenvironment that hosts and influence the behaviour and characteristics of stem cells
how did concept of niche emerge and the basic idea
- Scofield 1978
- Has a defined anatomical location.
- Regulates self-renewal and
- Removal from niche results in cellular differentiation
Niche example:
signals from Distal tip Cell (DTC) triggers the self renewal program in the gremlin stem cells
-as the cells divide some end up away from the DTC - lose niche signal and diff (mitosis)
Niches- concepts: OCCUPANCY
cell-cell adhesion between stem cell and niche locates SC’s niche, near to self-renewing signals
