Lec 6: Hematopoiesis Flashcards
What is a stem cell?
- early progenitor cell with the capacity to differentiate into mature cells
- potential to mature into a number of different cell types
- provides ‘raw material’ to repopulate cells that die (normal turnover), are killed, or are removed because of errors/injuries
Describe the stem cell hierarchy
totipotent -> pluripotent -> multipotent
Define totipotent.
the ability of stem cells to give rise to all embryonic and extra embryonic tissues
Define pluripotent.
the ability to give rise to all embryonic tissues, but not extra embryonic tissues
Define multipotent.
the ability to give rise to the diverse cell types of one or a few tissues
All of the cells of the immune system derive from?
a common hematopoietic stem cell in the bone marrow
How do HSC supply the entire repertoire of mature blood cells for the lifetime of an organism?
- self renewal capacity: maintains and expands stem cell pool
- multi-lineage differentiation potential: produces the diverse blood cell types of the mature hematopoietic system
Describe how stem cells produce more stem cells are progenitor cells?
- on each division, gives rise to another stem cell and a progenitor cell
- the progenitor cell is committed to producing related cells
- the greater the level of differentiation, the greater the level of commitment to a particular lineage (more restricted) and lower capacity to self renew
How can you differentiate between the various leukocyte populations?
- can do it at protein (surface or intracellular markers) or the gene (mRNA expression) level
- staining; label with antibodies/fluorochromes
Describe how flow cytometry works.
- anti CD19 (red)
- anti CD3 (green)
- mix them all up; some are green, some are red, some are nothing
- go one by one through detector and cells are sorted based on fluorescence
- can tell what cell types you have and proportion of cell types
How can you differentiate between the various leukocyte populations?
- can do it at protein (surface or intracellular markers) or the gene (mRNA expression) level
- staining; label with antibodies/fluorochromes
Describe how flow cytometry works.
- anti CD19 (red)
- anti CD3 (green)
- mix them all up; some are green, some are red, some are nothing
- go one by one through detector and cells are sorted based on fluorescence
- can tell what cell types you have and proportion of cell types
How can gene expression be used to answer questions about blood cells?
- is this cellular population expressing the genes we expect them to? (too much proliferation, mutated genes , high expression of inflammatory genes)
- does this tissue have high levels of a leukocyte specific gene?
- Can we identify why animal X responds well to a disease whereas another animal succumbs to the same challenge? (understand disease progression, genetics contribute to disease)
Among Q-PCR, microarrays and microarrays, which can study the most genes at one time?
microarrays > macroarrays > Q PCR
What is the hematopoietic microenvironment referred to as?
stem cell niche
What is the role of the hematopoietic microenvironment?
- stem cells need a nurturing environment
- these and other cells provide soluble growth factors
- environment drive or simply selectively help mature a responsive cell following event
- bone marrow stem cell niche helps maintain stem cell properties, including self renewing capacity and ability to differentiate into multiple lineages
- critical component for sustaining dormant (quiescent) stem cells
What are the 2 types of bone marrow and what is the difference?
- red marrow: actively generates blood cells
- yellow marrow: dormant; more fat cells
Why is the quiescent state an essential mechanism to protect stem cells from stress and sustain long term hematopoiesis?
- want dormant stem cells because mutations can occur if continues to proliferate (maintains integrity of genetic coding), as well as saving energy and may need in future
What does the bone marrow consist of?
- capillaries
- reticular fibres of connective tissue
- fibroblasts which secrete these fibres
- immature blood cells in all stages of maturation
- upon maturation these migrate through the endothelial cells that form the capillary walls into the blood stream
Why is the quiescent state an essential mechanism to protect stem cells from stress and sustain long term hematopoiesis?
- want dormant stem cells because mutations can occur if continues to proliferate (maintains integrity of genetic coding), as well as saving energy and may need in future
Stromal and other cells provide a nurturing environment through what 3 things?
- cell derived components (soluble growth factors, cell adhesion molecules, extracellular matrix molecules)
- systemic control factors (injury and neurohormones)
- physiological conditions (oxygen tension)
What are some other hematopoietic organs?
- some in adult tissues (migrating stem cells or local de novo hematopoiesis in brain)
- depends on species (bony fish kidney and spleen)
- depends on development stage
Stromal and other cells provide a nurturing environment through what 3 things?
- cell derived components (soluble growth factors, cell adhesion molecules, extracellular matrix molecules)
- systemic control factors (injury and neurohormones)
- physiological conditions (oxygen tension)
What are some other hematopoietic organs?
- some in adult tissues (migrating stem cells or local de novo hematopoiesis in brain)
- depends on species (bony fish kidney and spleen)
- depends on development stage
