Stem cells and cancer stem cells Flashcards
What are the different types of stem cell lineage?
- Totipotent - embryonic cells that can form the whole human, placenta and other tissues.
- Pluritpotent - Slightly older embryonic cells that can form every cell type of the body, but not the placenta.
- Multipotent - Stem cells commit down a certain range of related lineages and cannot naturally turn back into pluripotent cells or switch lineages.
What is an impotant characteristic of some stem cells in order to maintain stem cell longevity throughout life.
A small population of stem cells enter into quiescence
How are quiescent cancer stem cells sensitized for chemotherapy.
HDACs (histone deacetylases) before chemo may remove quiescent cancer stem cells from this state, making them a proliferative cell that can be targeted by chemotherapeutics.
What are the Yamanaka factors?
Oct4, Sox2, Klf4, c-myc. In vitro culture of skin cells reprogrammed these mature cells into pluripotent cells, capable of producing cells of all lineages. (induced pluripotent stem cells)
How was self-renewal of stem cells discovered?
- Lethally irradiate a mouse, left untreated it will die from a failure of its bone marrow.
- Treat the irradiated mouse by injecting bone marrow from a healthy donor.
- Bone marrow treatment rescues long term haematopoeisis.
How is it shown that bone marrow treatment rescues LONG term haematopoeisis?
In blood there are long term and short term haematopoeitic stem cells. Short term HSCs would regenerate the blood system for a few weeks but gradually disappear. Long term HSCs are the stem cells that can regenerate the blood system indefinitely. This is shown experimentally by their ability to perform in secondary and tertiary transplants. It demonstrates that there are long-lived stem cells that retain self renewal and the ability to repopulate the blood system.
What is a lineage tracing marker for stem cells found in the intestinal crypt>
Lgr5
What are three common techniques used for testing cancer stem cell potential?
Xenograft assay, Differentiation assay, Colony formation
How can sub-populations of cells containing CSCs be identified?
- Sub-cloning: separating the tumour in a way that gives rise to individual, single cells. Then produce clonal populations from those cells.
- Prospective isolation: Requires knowledge of the cells being investigated. If a surface antigen is known then FACS can be used (fluorescently tag antibodies specific to the marker of interest and then a machine sorts the fluorescent cells from the rest). Then transplant these cells Vs non marker cells into mouse models. If the marker positive cells give rise to tumours and the marker negative do not, this suggests the presence of a tumour initiating cell.
Following next generation whole genome sequencing of a tumour, what would be expected to be seen in a single gene readout if the genetic heterogeneity was monoclonal or polyclonal.
If it’s monoclonal, every readout will contain the mutation in the gene. If it is polyclonal, only a proportion of the DNA fragments will contain the mutation
What functional test is used to define if a population of cells are adult stem cells?
Whether or not they can regenerate a tissue (long term)
What are the two different models of stem cell production?
Hierarchial Vs stochastic
What is Heirarchical production of stem cells?
Every time the stem cell divides it produces another stem cell and a slightly more differentiated transit amplifying progenitor. The TA progenitor can go on to produce the differentiated cells of a tissue. Always has assymetric division of stem cells.
In what stem cell populations is heirachical production seen?
Neural stem cells, drosophila germline stem cells
What is stochastic stem cell replication?
Symmetrical division: Either the stem cell divides into two more stem cells or into differentiated progenitors. It requires balancing to ensure there is the right amount of stem cell maintenance as well as differentiated cell fates.
