SC and stress Flashcards
What does haematopoesis do?
hematopoesis - sustains production of all mature blood cells throughout life
What is the main site of homeostasis in adults?
main site of hematopoesis i adults is bone narrow (makes it difficult to study)
What can be a stressor for the hematopoetic system?
either malignancy is developing or a damage or inflammation
What is the effect of cytokines in the bone marrow?
cytokines during infection travel to the bone marrow and trigger emergency replenishments
Is the inflamatory response cell speecific?
inflammatory response induces production of new cells and this response tends to be cell type specific, for example some bacteria tend to specificly increase the number of neutrophiles in the blood
Where do cytokines act and what’s the result of it?
cytokines act throught the hematopoetic cascade so the reaction can be rapid contrary to when they would only react on stem cells
Why is it difficult to identify the stem cells in the bone marrow?
bone marrow is a complex tissue that consists of many cell types and is also spanwith thin blood capilaries to which newly made blood cells can escape. Because of the complex structure it is almost impossible to identify the precursors of the mature blood cells and the stem cells as they do not have any particulkar characteristics that could be easily identified
How can you assay for presence of hematopoetic stem cells?
- when an animal is exposed to a large dose of X-ray radiation most of their hematopoetic cells are destroyed and the animal dies within a few days as a result of their inability to manufacture new blood cells. The animal can be saved by a transfusion of cells taken from a bone marrow of a healthy donor. This is can we can assay for the presence of hematopoetic stem cells and hence discover the molecular features that distinguish them from other cells
- For this purpose, cells taken from bone marrow are sorted (using a fluorescence-activated cell sorter) according to the surface antigens that they display, and the different fractions are transfused back into irradiated mice. If a fraction rescues an irradiated host mouse, it must contain hematopoietic stem cells. In this way, it has been possible to show that the hematopoietic stem cells are characterized by a specific combination of cell-surface proteins, and by appropriate sorting we can obtain virtually pure stem-cell preparations
Why is it good to keep the division rate of stem cells low?
-lower rate of division means that fewer mutations are accumulated overtime
- decreases the rate of divisional cell senescence
Why can you grow progenitor cells dispersed in culture but not HSCs?
While the stem cells depend on contact with bone marrow stromal cells for long-term maintenance, their committed progeny do not, or at least not to the same degree. These cells can thus be dispersed and cultured in a semisolid matrix of dilute agar or methylcellulose, and factors derived from other cells can be added artificially to the medium. The semisolid matrix inhibits migration, so that the progeny of each isolated precursor cell remain together as an easily distinguishable colony. A single committed neutrophil progenitor, for example, may give rise to a clone of thousands of neutrophils.
What are colony stimulating factors?
Suchculturesystemshaveprovidedawaytoassayforthefactorsthatsupporthematopoiesisandhencetopurifythemandexploretheiractions.Thesesubstancesareglycoproteinsandareusuallycalledcolony stimulatingfactors(CSFs).Someofthesefactorscirculateinthebloodandactashormones,whileothersactinthebonemarrowassecretedlocalmediators;stillotherstaketheformofmembrane-boundsignalsthatactthroughcell–cellcontact.
Is commitment a rapid process?
commitment is a stepwise process; stem cells go through a wide range of steps becoming more and more restricted; firstly they commit to either the myeolid of lymphoid fate which then gives rise to a wide range of progenitors
What happens to HSCs during stress?
when there is stress the hsc become actiated and a large number of them are now entering the cell cycle
Why can you keep the population of hematopoetic stem cells relatively low?
Hematopoietic progenitor cells generally become committed to a particular pathway of differentiation long before they cease proliferating and terminally differentiate. The committed progenitors go through many rounds of cell division to amplify the ultimate number of cells of the given specialized type. In this way, a single stem-cell division can lead to the production of thousands of differentiated progeny, which explains why the number of stem cells is such a small fraction of the total population of hematopoietic cells.
What can CSFs control?
- CSFs are factors that promote the production of differentiated blodod cells ; they can control:
- rate of cell division
- the number of cell division cycles that the progenitor cell undergoes before differentiating
- in might act late in the hematopoetic lineage to facilitate differentiation
- it might act early to influence commitmenent
- it might increase cell’s probability of survival
What is the evidence that behaviour of hematopoetic cells depends partly on chance?
studies in vitro indicate that there is a large element of chance in the way a hematopoetic cell behaves - a reflection presumably of noise in the genetic control system (if two sister cells are taken immediately after cell division and cultured apart under identical conditions they fraquently give rise to colonies that contain different types of blood cells or the same ytypes of blood cells in different numbers) → both commitment and differentiation seem to involve random events at the level of individual cell eventhough the regulation of the multicellular system as a whole is quite reliable
What is Sca 1 important for?
Sca 1 is important for the reaction with interferons, it gets activated by interferon
How can you check if your cells are HSCs?
You can do a functional assay to see if the cells you chose are actually HSCs
What is the HSC heterogeneity?
you don’t always see the same
every HSC can give you different results (biased reconstitution)
What can be the source of heterogeneity in HSCs?
differential genetic and epigenetic reprogramming during early development and cell maturation, (b) differential localization in BM niches, and (c) genetic and epigenetic reprogramming brought on by responses to different molecular and cellular stimuli
