Week 10 Flashcards
(17 cards)
What are some phenotypic features of Down Syndrome in Humans?
- Craniofacial abnormalities
- Cardiac defects
- Intellectual disability
- Increased risk of Alzheimers
- Increased risk of leukemia
How is the risk of a developmental disorder calculated?
- Risk is calculated by taking into account the risk due to the woman’s age with the risk estimated from serum levels of various biochemical markers
What are the 4 markers tested from in maternal sera?
- Alpha fetoprotein
- Unconjugated estradiol
- hCG
- Inhibin A
How can the karyotype of a feotus be determined in utero?
- Amniocentesis
2. Chorionic villus sampling
What causes Down Syndrome?
- Trisomy of chromosome 21
- Specifically the altered copy numbers of certain dosage-sensitive genes
- The over-expression of these genes causes the Down Syndrome phenotype including:
- Intellectual disability:
- DYRK1A
- Synaptojanin 1
- SIM2
How is Down Syndrome modelled in mice?
- Trisomy 16 mouse (Ts65Dn mouse)
What therapeutic outcomes have been uncovered using the Ts65Dn mouse model?
- Treatment of Ts65Dn mice with Fluxoetine improves adult neogenesis in the hippocampus which may help with intellectual disability
- Treatment of Ts65Dn mice with neuroprotective peptides has been shown to reduce developmental delays in achieving a number of sensory and motor milestones
- Treatment with picrotoxin has reduced intellectual disability in these mice also
- The amyloid precursor protein (APP) is localised to chromosome 21 so these mice can also be used to study Alzheimers
What are the defining properties of stem cells?
- It is not itself terminally differentiated
- It can divide without limit
- When it divides it can form either another stem cell or a cell that embarks on terminal differentiation
- Divisional asymmetry can be due to either internal (inherited) or external (environmental) factors
e. g. Numb protein causes cells to retain stemness whilst notch protein causes the daughter cell to differentiate
What is a stem cell niche?
- A stem cell niche provides signals to stem cells to help regulate the balance between self-renewal and differentiation (can inhibit or stimulate environmental asymmetry
- The basic model of a stem cell niche includes:
1. Stem cell is attached via adhesion molecules to a basement membrane
2. Niche cells near the stem cells secrete signals that influence how a stem ell behaves
3. The stem cells can divide parallel to the basement membrane producing an adhered daughter cell that is stem or it can divide perpendicular to the basement membrane and produce a daughter cell that is differentiated
Name key niche (extrinsic) and cell autonomous (intrinsic) signals that regulate intestinal stem cells
Extrinisic:
Niche signals (Wnt and Notch) regulate the proliferation and differentiation of intestinal stem cells
1. Wnt Pathway:
- The Wnt signalling pathway is activated in the crypt and not activted in differentiated cells
- A secreted factor
- Excess Wnt can lead to tumour formation
- Notch Pathway:
- Notch is retained in the membrane
- Determines which cells will be secretory and which will be absorptive
- Notch is activated in absorptive cells and inactive in secretory cells
- If Notch is switched off the intestine will contain only secretory cells - Intrinsic:
- Snai1 is needed for intestinal stem cells
List types of stem cell niches present in the body:
- Bone marrow
- Intestinal crypt
- Mammary gland
Give an example of adult stem cell therapy:
- Bone marrow transplants
Describe ES cells how they are derived
ES cells:
- Can be obtained from ICM of blastocyst or primordial germ mass of fetus
iPS cells:
What is therapeutic cloning?
- A means of producing patient specific pluripotent stem cells
- Involves placing the nucleus of a terminally differentiated somatic cell into a anucleated unfertilised egg
- The ES cell lines are genetically identical to the donor nucleus DNA
Describe potential therapeutic applications of ES cells and some of their limitations:
- Macular regeneration
- Cardiac muscle regeneration
Limiting factors:
- Immune rejection
Describe potential therapeutic applications of ES cells and some of their limitations:
- Macular regeneration
- Cardiac muscle regeneration
Limiting factors:
- Immune rejection
- Can form tumours
- Ethical issues
Describe how iPS cells are derived and the pros and cons of using them therapeutically:
- iPS cells are derived from somatic (epithelial) cells that are exposed to key transcription factors that make them pluripotent:
1. Oct4
2. c-myc
3. Sox2
4. Klf4
Pros:
- Patient specific
- No ethical issues
- Could be used as treatment for disease such as Type I diabetes
- Can be used to make models
Cons:
- Can form tumours
