Stem cell and blood cancer Flashcards
why is the difference between a progenitor and a stem cell very important for blood transplant?
- if you get given a progenitor you will die very quickly but if you get given a stem cell you will live hopefully
what is the association between twins and leukaemia?
This disease starts before children are born. This was found from looking at twins. If you have twins which share placentas and this placenta has a cells which develops a pre-leukaemic cell and this is a stem cell and is self-renewing, then both cells are getting them and both will inherit these cells. This does not necessarily mean that both children will get it as there are many genetic events which compound to produce leukaemia.
how many times is blood formed in development?
twice - blood in the yolk sac is replaced and doesn’t have stem cells and is replaced by blood that have stem cells
how can you use iPSC to look at leukemia?
you can make an iPSC blood stem cells with the leurkamia mutation and then add lots of different mutations and you can look at which ones cause cancer
why is blood cancer in the adult so much worse than blood cancer in children?
when these waves of cells in the first group of blood cells, the mutations aren’t related to stem cells- this set of cells does not contain stem cells. SO when these cells develop cancer like mutations, the cells don’t actually have very cancer harbouring activities. These cells are destined to die. Whereas if you get an oncogene in adults which is related ot stem cells, then this is much harder to treat and more aggressive.
why is asymmetrical cel division so important for blood transplant?
need to be able to increase in number
why is the hieracichal system safe?
- if you put a mutation in the stem cell it will repopulate the entire system but a mutation further down is less harmful
what was phil jones’ idea?
came up with the idea that progenitors “throw a dice” and once this reaches a critical point- a clone will stay alive and you can maintain the progenitor cell pool.
- 80% of the time they will asymmetrically divide and 10% the rest of the time they will either symbiotically into progenitor or into differentiated- this means that one progenitor only have to to do a certain number of asymmetrical or progenitor symmetrical to always be present and maintain the entire system
how can you look at the way the stem cel lineage is dividing, what does this show?
you use a transposon mobilisation in stem cells, you can mark every cell differently and in vivo you can read out whats normally happening- there is very little evidence for multipotent stem cells contributing to the blood lineages- they are all being porduced from independent cells. And when you transplant then you go back to the stem cell model.
how were studies of the oesophageal epithelium interesting?
- they stained for stem cell makers and there were non: they were all functionally equivalent and homogenous
- all cells seemed to be diving at a similar rate
- they looked at the ability of each cell to cycle and produce differentiated progeny using the loxp cre system and found that the number of clones per 100 cells decreased and that those clones that remained increased in size over time (dont get this!). studies of interfollicular peidermic revealed that this pattern of clonal evolution was consistent with progenitors dividing stochastically to generate differentiated and cycling duaghters with equal porbability
what was condlusded about he OE?
n summary, these results show that EE is both maintained and repaired by a single progenitor cell population capable of reversibly switching between homeostatic and regenerative behavior in response to injury. not supported by a discrete slow-cycling stem cell population
what happened to the OE when exposed to injury
They labelled cells and exposed them to something that would incudce an injury response. This showed that rates of proliferation increased and the formation of layers of differentiated cells. There was no significant change in the proportions of symmetric and asymmetric divisions, which indicated that the treated tissue was homeostatic.
what studies were carried out in the murine epidermis to suggest that the progenitor situation was the same as in the OE?
cells were studied by producing a transgenic line which expressed YFP with a stop codon floxed, preventing its transcription. This line was crossed with a tmx-inducible CRE line. this alloed cells expressing cre, and theit progeny, to be labelled and tracked over time. Initially, labelled cellss were only present 1/600 cells in the basal layer after 2 days. The number of labelled cells then increased over time- almost certainly from the preveiously, rare single cells.
the labelling also showed cells that stayed cohesive (stayed together) and expanded progressivley in size.
the number of clones increased over time and then clone numbers began to fall with clonal loss through differentiation.
- he cells did not come from the hair follicle bulge stem cell pool as this region was not labelled.
- the immunostaining of clones consisting of two basal cells reveals that s ingle cell division may generate either one cycling and non non-cycling duaghter or two cycle duaghters or two non-cycling daughters
why is it scar is the progenitor theory is true?
- once divides a certain amount of times it can never be ridden of
describe what a study found about blood formation!
Here we have established a novel experimental model in mice where cells can be uniquely and genet- ically labelled in situ to address this question. Using this approach, we have performed longitudinal analyses of clonal dynamics in adult mice that reveal unprecedented features of native haematopoiesis. In contrast to what occurs follow- ing transplantation, steady-state blood production is maintained by the successive recruitment of thousands of clones, each with a minimal contribution to mature progeny. Our results demonstrate that a large number of long-lived pro- genitors, rather than classically defined haematopoietic stem cells, are the main drivers of steady-state haematopoiesis during most of adulthood. Our results also have implications for understanding the cellular origin of haematopoietic disease.
