lecture 15: stem cells – basic concepts Flashcards
1
Q
What happens between blastocyst and foetus stage?
A
- cell determination
- cell proliferation
- cell differentiation
- patterning and morphogenesis
- programmed cell death
2
Q
What happens during embryogenesis?
A
- cells become restricted in their developmental capacity
- Morula
- trophectoderm
- inner cell mass → ES cells
- primitive endoderm
- parietal endoderm
- visceral endoderm
- primitive ectoderm
- epiblast
- definitive endoderm → liver, pancreas, lung
- mesoderm → blood, heart, skeletal muscle
- ectoderm → CNS, skin
- germ cells
- epiblast
- primitive endoderm
3
Q
How do determination and differentiation occur?
A
- result not from changes in genes, but from changes in gene expression (exception; immune system and gametes)
- results from alterations in chromatin structure and transcription factor expression
- often quite permanent and heritable through many cell divisions
4
Q
What is determination?
A
- occurs prior to overt differentiation – a heritable change in a cell’s developmental potential-operationally defined
- may not be able to visually see differences in the cell
- e.g. multipotent cardiovascular progenitors
5
Q
What is differentiation?
A
- result of changes in gene expression
- cell acquires correct shape polarity, orientation with respect to neighbours, appropriate organelles and proteins which enable it to carry out metabolic signalling, transport or contractile functions required in a particular tissue
6
Q
What is transdifferentiation?
A
- de-differentiation
- cell normally committed to one lineage is switched to a different lineage pathway
- many known examples from disease states – intestinal metaplasia of the oesophagus, squamous metaplasia in the respiratory tract or bladder
- may be induced experimentally by ectopic expression of master regulator transcription factors
7
Q
What are possible examples of transdifferentiation between cells in two closely related lineages?
A
- oval cell progenitor → hepatic oval cell
- bile duct
- hepatocyte
- pancreatic oval cell → hepatocytes
- two very closely related tissues in development
- distinct in terms of function but capable of interconversion
8
Q
What is intestinal metaplasia?
A
- damage to oesophageal epithelium through acid reflux from the stomach leads to conversion of squamous epithelium into intestine
- the condition is a precursor to oesophageal adenocarcinoma
9
Q
What is developmental capacity?
A
- a multipotent cell can give rise to several types of mature cell
- a pluripotent cell can give rise to all types of adult tissue cells plus extraembryonic tissue: cells which support embryonic development
- a totipotent cell can give rise to a new individual given appropriate maternal support
- restricted up to about 4- to 8-cell stage of development
10
Q
What are adult tissues?
A
- continuously renewing - bone marrow, skin, gut
- conditionally renewing - liver, kidney
- non-renewing - cardiac muscle
11
Q
What is cell turnover in the adult body?
A
- we lose 20 billion cells per day
- the lining of the intestine is replaced every four days
- every 4 weeks a completely new epidermis is generated
- some tissues turn over slowly - hepatocytes live for 300 days, cardiomyocytes 0.5% annually
- needs to be done very precisely
12
Q
What is a stem cell?
A
- a primitive cell which can either self renew (reproduce itself) or give rise to more specialised cell types
- stem cell is the ancestor at the top of the family tree of related cell types
- one blood stem cell gives rise to red cells, white cells and platelets
13
Q
Where are tissue stem cells located?
A
- skin: replaced by stem cells deep in the tissue - the basal layer, cells in the middle undergoing maturation process, stratum corneum at the top
- hair: follicle, region called the bulge is where stem cells live and are responsible for this constant turnover
- intestine: paneth cells
- blood
14
Q
What are stem cells?
A
- capable of self renewal or differentiation
- may give rise to transit amplifying cell compartment-committed cells with limited division capacity
- often lacking in specialised organelles, and show high nucleus/cytoplasm ratio
- long lived – express telomerase
- slowly dividing
- few in number
- may be restricted spatially to specific zones or niches
- respond to signals which will regulate their growth and proliferation, enabling them to meet changing demands
- e.g. when someone is undergoing chemotherapy
- often own bone marrow will be ablated
- has to be replaced or the patient will die
- can be done by infusing just a few stem cells
- will grow back and repopulate the entire blood forming system → stem cells, mature cells, etc
- dramatic example of how a normally quiescent cell can undergo this massive degree of expansion
15
Q
What are tissue stem cells?
A
- proper tissue organisation and response to demands of growth or repair require that there be restrictions on developmental potential of adult stem cells
- these limits are strictly imposed by powerful molecular restraints on gene expression and are heritable during many rounds of cell division
- an adult stem cell may show relaxation of these restrictions in an altered environment, possibly accounting for plasticity
- even so, plasticity is observed usually at low frequency
16
Q
What is proof of stem cell isolation?
A
- a single cell can repopulate a tissue and give rise to differentiated progeny as well as more stem cells
- identified in transplantation assays with marked cells
- critical that descendants of stem cell are shown to be functional
17
Q
What are markers of specific differentiation stages in cell lineages?
A
- transcription factors
- cell surface molecules (e.g. CDs)
- cytostructural molecules e.g. intermediate filaments specific functional gene products
- specific functional gene products