in vivo Stem Cells Flashcards
What is meant by stem cell potency?
The ability to differentiate into different cell types.
What is a stem cell niche?
A microenvironment surrouding stem cells that regulates whether the stem cells should self-renew or differentiate.
What are the two types of cell regulatory mechanisms?
Extracellular and intracellular regulatory mechanisms
What are the two types of extracellular regulatory mechanisms?
Physical and chemical
2
Give examples of physical extracellular regulatory mechanisms.
- Structural and adhesion factors within extracellular matrix support cellular architecture of the niche
- Mechanical forces influenced by cell-to-cell and cell-to-matrix adhesion and cell density
3
Give examples of chemical extracellular regulatory mechanisms and briefly describe their purpose.
Endocrine, paracrine and juxtacrine mechanisms usually keep stem cell in uncommitted state and movement away promotes differentiation.
3
Give examples of intraacellular regulatory mechanisms.
- Regulation by cytoplasmic determinants
- Transcriptional regulation
- Epigenetic regulation
Describe regulation by cytoplasmic determinants.
As a stem cell divides, factors determining cell fate are either selectively partitioned t one daughter cell or shared evenly between daughter cells.
Describe transcriptional regulation of stem cells.
Occurs through a network of transcription factors that keep a stem cell in a quiescent or proliferative state and promote maturation of daughter cells toward a certain fate.
Describe epigenetic regulation of stem cells.
Different patterns of chromatin accessibility influence gene expression related to stem cell behaviour.
Give two examples of stem cell niches in the fruit fly.
- Drosophila testes
- Drosophila ovaries
4
What are fruit flies considered the supermodel of biology?
- Fast reproductive rates
- Excellent genetic tools
- Well characterized genome
- ~75% of known human disease genes have a match in the fruit fly
In what organism was the Hippo signalling pathway first discovered?
Fruit fly
What is called “The Hub” in the Drosophila testes niche?
12 somatic testes cells surrounded by 5-9 germ stem cells
How does division occur in the Drosophila testes germ stem cells?
Asymmetric division of the GSCs such that one cell remains attached to The Hub and one unattached cell
In Drosophila testes, what happens to the attached daughter cell after division?
Receives high levels of Unpaired protein
What is the role of Unpaired protein in the Drosophila testes niche?
Binds to receptors on GSCs and activates the JAK/Stat pathway to specify self-renewal
What happens to the unattached daughter cell following division in the Dros. testes niche?
Becomes a gonialblast and receives low levels of Unpaired protein
What is a gonialblast?
Sperm cell precursor
What are Drosophila oocytes derived from?
GSCs held in the ovarian stem cell niche
Describe division of GSCs in the D. ovarian stem cell niche.
GSCs are in contact with Cap cells.
Following division, one daughter cell remains tethered to the Cap cell by E-cadherin and maintains self-renewal identity while the other cell is displaced and begins oocyte differentiation
Describe paracrine signalling regulation in the D. ovarion stem cell niche.
Cap cells produce TGF-beta, proteins that activate BMP signal transduction pathways in GSCs, preventing differentiation.
Describe how extracellular matrix components contribute to regulation of the D. ovarian stem cell niche.
Collagen and proteoglycans prevent TGF-Beta diffusion such that only the tethered cells receive significant amounts of the TGF signals.
What transcription factors regulates differentiation in the D. ovarian stem cell niche?
Bag of marbles (bam)
How does bam work?
Activation of the BMP signal transduction in GSCs represses transcription of bam
When bam is expressed, the cell begins to differentiate into an oocyte
What tethers the GSCs in the D. ovarian stem cell niche to Cap cells?
E-cadherin adherens junctions
