Tissue renewal, stem cells + cancer Flashcards
Cancer cells have defects in which 2 types of gene?
Activating mutations in porto-oncogenes
–> oncogenes
Inactivation of anti-proliferation genes
–> tumour suppressors
Give 2 examples of tumour suppressors
What happens if they’re lost/inactivated?
Rb
CIP
Results in inappropriate progress into S phase
In the skin, which direction do cells move when they become more specialised?
From the dermis towards the epidermis
Which layer of the skin is a continually renewing barrier?
Epidermis
What are the 3 key factors to maintain tissue organisation?
Cell communication
Selective cell-cell adhesion
Cell memory
What is selective cell-cell adhesion?
Presence of specific cell adhesion molecules allow organisation of cell layers
What is cell memory?
Cell has a ‘memory’ of its developmental history
- dictates which set of genes it expresses + this allows it to perform its specialised function
Which cells are renewed... > never? > yearly? > monthly? > daily?
Neuron
Bone
Epidermal + erythrocyte
Gut epithelial
How do stem cells proliferate to renew tissues?
> Self-renewal
> Generate intermediate precursor cells that divide a few times before producing differentiated cells
Where in a blastocyst are embryonic stem cells found?
Inner cell mass
What are oligopotent stem cells?
Cells that give rise to a few terminally differentiated cell types
Describe the structure of epidermis
Basal cells - including stem cells + dividing precursors - sit on basal lamina above the dermis
Describe how epidermis is renewed
Dividing precursors divide 2-3 time before they differentiate
- gain expression of adhesion molecules specific to the supra-basal layer
–> pulled up into supra-basal layer + lose capacity to divide
- > continue to move upwards, become flattened + dehydrated
- nucleus etc. breaks down
Cells sloughed off at surface
Describe the structure of gut epithelium
Single cell layer
Folded into crypts + villi
Stem cells reside at base of crypt
Describe the renewal of gut epithelium
Stem cells at base of crypt give rise to dividing precursor cells
- > slide up towards villus tips
- > differentiate to form secretory + absorptive cell types needed
Cells lost at tips of villi
What is the name of the pathway that controls stem cell renewal + production of diff cell types?
What happens when this pathway is active + inactive?
Wnt pathway
Active = cell proliferation
Inactive = no cell proliferation
What do all blood cells come from?
A single type of multipoint hematopoietic stem cell in bone marrow
What have stem cell therapies been used to treat?
How is this carried out?
Blood disorders
e.g. leukaemia
Destroy patients own bone marrow cells by radio-/chemotherapy
-> replace bone marrow by transplantation of donor bone marrow
= replaces blood stem cell pool
What are iPS cells?
Differentiated cells reprogrammed into stem cell state using TFs
What are human iPS cells used for?
Providing an ethical replacement for hES cells:
> disease remodelling + toxicology
> regenerative medicine
What are the 3 key genes that can convert a differentiated cell into an iPS cell?
Sox2
Klf4
Oct4
Describe how a benign tumour forms
How is a malignant tumour formed?
- Mutation gives 1 cell a growth advantage
- 2nd mutation increases the advantage
- 3rd mutation increases advantage further + makes cell invasive
Cells invade surrounding tissues
-> leads to damage that may be life-threatening
What are metastasis?
Development of secondary malignant growths at a distance from a primary site of cancer
How can a polyp in the gut epithelium lead to malignant cancer?
1. Tumour suppressor gene (APC) lost = excessive epithelial proliferation 2. Oncogene (Ras) activated =small tumour 3. Another TS gene lost = large tumour 4. 3rd TS gene (p53) lost = tumour becomes invasive 4. Rapid accumulation of mutations = metastasis
