Tissue/adult stem cells Flashcards
What is an adult stem cell?
A stem cell present in adult tissues/organs that retains the characteristics of stem cells i.e. self-renewal and potency, except that adult stem cells are usually unipotent or multipotent
What is cellular homeostasis? (2)
- The constant/periodic generation of new cells to replace old, damaged and dying cells or the addition of new cells as needed
- Adult stem cells fulfil this role through regeneration/replacement
How do stem cells divide asymmetrically? (3)
- One daughter cell is another adult stem cell
- Other daughter cell is a transit-amplifying (progenitor) cell which rapidly proliferates and they differentiate
- Differentiated cells go on to repair damage
What is a stem cell niche?
A specialised, tissue-specific microenvironment that regulates adult stem cells
What are the 2 main components of a stem cell niche?
- Physical
- Chemical
What are the physical aspects of a stem cell niche? (2)
- Cell adhesion
- Extra-cellular matrix
What are the chemical aspects of a stem cell niche? (2)
- Secreted proteins (signalling molecules)
- Metabolic molecules (Ca2+, ROS)
What intracellular mechanisms regulate adult stem cells? (3)
- Epigenetic regulation
- Transcriptional regulation
- Cytoplasmic determinants
What is epigenetic regulation of stem cells?
Histone modifications and methylation influence the expression of stem cell genes
What is transcriptional regulation of stem cells?
Networks of transcription factors regulate stem cell quiescence, proliferation, differentiation and self-renewal
What is quiescence?
Inactivity/dormancy
What is cytoplasmic regulation of stem cells?
Asymmetric distribution of proteins govern the mode of cell division
What is the stem cell niche for the germline stem cells in drosophila?
The germarium within the ovarioles
How does germline stem cell differentiation occur in drosophila? (3)
- 2 germline stem cells in each germarium which are tightly associated with cap cells via E-cadherin adherens junctions
- Germline stem cells divide asymmetrically forming one self-copy and one cystoblast cell
- Cystoblast cell does 4 rounds of cell division and 1 out of the 16 cells becomes the oocyte
How is the germline stem cell maintained in drosophila? (3)
- Cap cells secrete TGFβ which binds to receptors on the germline stem cells and activates BMP signalling
- bam gene is suppressed which is required for differentiation
- Close association of cap cells and germline stem cells via adherens junctions required
How does germline stem cell differentiation occur in drosophila? (2)
- Asymmetric cell division means one of the daughter cells moves away from the cap cells and TGFβ secretion
- No BMP signalling occurs in the cell so bam is no longer suppressed so differentiation can occur
What is the equivalent of BMP signalling in drosophila?
dpp
What happens to drosophila germline stem cells when you lose BMP signalling/overexpress bam?
Differentiation
What happens to drosophila germline stem cells when you overexpress BMP signalling/lose bam?
Germline tumours (too much stem cell self-renewal)
What are satellite cells?
Skeletal muscle stem cells
Where is the stem cell niche for skeletal muscle stem cells?
Between muscle fibre and basal lamina
How do skeletal muscle stem cells respond to damage? (4)
- Reside in G0
- Damage causes them to activate and enter the cell cycle
- Generate progenitor cells which differentiate and repair damage
- Stem cell pool is maintained
How are skeletal muscle stem cells maintained? (4)
- Apical-basal asymmetric cell division
- Par1 accumulates on the basal side and suppresses par3 which accumulates on the apical side
- Par3 in the apical cell activates p38 MAPK which induces myoD transcription
- MyoD drives differentiation so the apical cell becomes muscle and the basal cell is maintained as a stem cell
What is the importance of ECM/basal lamina remodelling in the skeletal muscle stem cell niche? (3)
- Satellite cells secrete MMP2/9 in response to damage which digests the ECM
- Satellite cells start synthesising laminin α1 instead of α2
- Laminin α1 is required for asymmetric distribution of par proteins
What are the therapeutic advantages of adult stem cells? (5)
- Already specialised so induction of differentiation into specific cells is easier
- Plasticity
- No immune rejection in autologous transplant
- No risk of teratomas (unlike embryonic stem cells)
- No ethical controversy
What are the therapeutic disadvantages of adult stem cells? (4)
- Limited quantity
- Limited lifespan in culture
- If isolated from aged individuals they may carry genetic damage due to ageing
- Potential of rejection if donor cells are from another individual
