Stem Cells Flashcards
Stem cells; what are they
- stem cells are unspecialized cells; not differentiated and have capacity to give rise to many things depending on potency
- can reproduce itself indefinitely; immortal
- under right conditions, can go through differentiation; at the end of differentiation it a specialized cell and no longer stem cell
Stem cells property: making a choice
After cell division of a cell; the stem cell has a choice to make based on factors (we didn’t learn yet) that influence which path it takes
-path 1: self renewal: stem cell has a daughter cell that becomes a stem cell to maintain stem cell population
path 2- stem cell has a daughter cell that goes to terminal differentiation
One route a stem cell can take to make a choice on its daughter cell when it divides: divisional asymmetry
- A factor that influences whether when a stem cell divides, whether it produces stem cells or differentiated cells is a determinant.
- The determinant is in a localized department within the cell, and when the stem cell divides, the determinant only is in one of the stem cells.
- The daughter cell that have the determinant is the one that stays a stem cell and can go through self renewal
- the daughter cell that doesn’t have the determinant becomes a terminally differentiated cell
- so you have one stem cell and one less plastic terminally differentiated cell as daughter cells bc of the asymmetry of the localized determinant when the stem cell divides
- This factor of the determinant leading to divisional asymmetry leads there to a bigger proportion of terminally differentiated cells as the terminally differentiated cells can also divide to make terminally differentiated cells, while the stem cells produce one stem cell and one terminally differentiated cell, making there be more terminally differentiated cells
Another route a stem cell can take to make a choice on its daughter cell when it divides: independent choice
- Independent choice is an alternative approach a stem cell can take when dividing.
- Independent choice means the daughter cells choice whether they want to be a stem cell or a differentiated cell based on environmental factors
- this results in more diversity as it can lead to daughter cells both being stem cells, one being a stem cell and one being terminally differentiated cell or both being terminally differentiated cells
- after the second round of division with the daughter cells (whichever of the three scenarios they pick), their daughter cells also vary as it isn’t like ashmmettric division.
- so the two stem cells daughter cells from first divsion can have daughter cells that range from all being stem cells to all being terminally differentiated cell and everything in between
- the one stem cell and one terminally differentiated cell will have two terminally differentiated cells, as terminally differentiated cell can only create terminally differentiated cell, but the stem cell can yield any of the three options discussed earlier
- the two daughter cells that are both terminally differentiated cell will only make terminally differentiated cells
Stem Cells of Animals
when stem cells divide, they make a choice in whether their daughter cells will be stem cells or progenitor cells (the two ways they decide is by asymmetric division (based on localized determinant) or independent choice (daughter cells choose based on environmental factors)
- the progenitor cells have gone through the change that they are not as plastic as stem cells; don’t look like them either
- once we have the progenitor cell, there are a few different pathways they can through
- depending on the type of stem cell, it can give rise to downstream terminally differienced cells; such as fat cells, bone cells, WBC
- stem cells have the capacity to give rise to a particular cell type that is found within the body of an animal
- so goes form stem cell, to progenitor cell and then downstream of that can be terminally differentiated cell, such as fat cell, bone cell, or WBC
Embryonic and Adult Stem Cells
- Embryonic Stem cells are pluripotent; this means that they can differentiate under different conditions to be any cell in the body bc it can create all germ layers; endoderm, mesoderm, and ectoderm; but they are totipotent so cannot generate more embryonic cells/tissue (can’t make placenta)
- Adult stem cells are multipotent; can generate a limited number of cell types; ex. a hematopoietic stem cell (gives rise to diff types of blood cells, cannot generate liver cells or kidney cells (embryonic stem cells can!)
ex of adult stem cell: hematopoiesis
- hematopoiesis are adult stem cells that give rise to cells needed for blood; such as plasma cells, neutrophils, basophils etc.
- it is a adult stem cell so it is multipotent, meaning it has restrictive differentiation capacity, usually results in production of cells of the tissue in which they reside (this is in blood marrow –> making cells from stem cells for blood)
- multipotent hematopoietic stem cells will go through cell division; some will be adult stem cells; some will differentiate
- the ones that will differentiate can go through two different types of pathway in this example, with commitment being made to either myeloid pathway or lymphoid pathway as it differentiates to what I believe is a progenitor (it is differentiated to either a lymphoid or myeloid pathway, so more differentiated than stem cell but not yet an actual lymphoid or myeloid so not terminally differentiated yet)
- both these differentated pathways gives rise to meyloid based cells and lymphoid based cells
- the steps of commitment correlate with changes in the expression of certain types of regulators found within the cells that are needed to produce diff subset of blood cells (changes in regulators result in which differentiated pathway it will take to produce either myeloid based cell or lymphoid based cell as they’re the components of blood)
- goes down one of two pathways (lymphoid of myeloid and then in those pathways there’s several steps of progressive restriction to get down to the actual cell- more and more specific with what the cell is going to be
power of stem cells: experiment using mouse and adult stem cells from bone marrow
- mouse was radiated with radiation that stopped the blood cell production; erythrocytes/RBC have lifespan of 120 days so it needs stem cells to make new blood cells
- without treatment, mouse will eventually die as the blood cells no longer being created as stem cells no longer differentiated in bone marrow as blood cell production stopped
- if mouse is given bone marrow from a healthy donor, the stem cells from there are able create blood cells and a small fraction of stem cells that are always there as the stem cells can do the downstream pathway once again and produce terminally differentiated cells (WBC/RBC) for the blood
- important point: even if there are a small population of hematopoatic stem cells that are upstream in the process of hematopoiesis (haven’t differentiated yet) they have the capacity to produce all the downstream blood cells that the mouse needs
- the mouse will now live
- shows the importance of adult stem cells in cells that have high turnover rate and need to be maintained such as blood for hematopoiesis
Another stem cell property: immortal
stem cells will keep on dividing bc they are telomerase positive, so they have telomerase to extend the telomeres each time it gets too short so it can never reach senescence and therefore continue with cell division forever
- this is good bc we need to be able to produce cells with high turnover rates with stem cells that are needed in the body, so stem cells are always needed
- however, could potentially be a drawback as if there’s a mutation or change within the stem cell, the stem cell already has telomerase expression to keep on dividing- connection to cancer
Cancer and Stem Cell Theory
It is theorized that a stem cell that has two mutations and becomes a cancer cell, only that cell if it is isolated will form a tumor cell. Since all stem cells have
- The other cells around it are differentiated and will not form a tumor cell
- theory is that the source of tumors may be form cancer stem cells, or they they can maintain cancer is a slightly diff way as they’re going to have a stem cell pool that’s constantly self renewing bc of positive telomerase
cloning animals: nuclear transplantation
an experiment was done with an enucleated egg cell that was radiated with UV. This caused damage to the cell and resulted in an enucleated egg cell. there was two diff nucleus that was inserted (in tow separate enucleated egg cells) to see which one would turn into tadpole.
- the first was from a grog embryo that was slightly differentiated (shep said not to refer to this slightly differentiated cell automatically as progenitor cell bc you have to look into protocol, just know its not a stem cell anymore) and was out in enucleated egg cell. the egg cell was able to develop into tadpole = experiment successful
- the second nucleus donor came from fully differentiated intestinal cell (was an adult stem cell before it became terminally differentiated) and was put into enculeated egg cell. The result was that most egg cells one activated to begin development stopped developing before tadpole stage.
- This experiment showed the impact of differentiation as well as I think embryonic cells vs previously adult stem cells. Bc the first part is that it cannot be fully differentiated and be a donor and expected to do the role of the nucleus when already differentiated within the cell. The second part is embryonic vs. adult stem cell. Even tho the intestinal cell is not an adult stem cell anymore, I THINK (not sure) that even if it was an adult stem cell but for a specific location, so for the intestine (how this intestinal cell was before it was differentiated), it wouldn’t be able to do the role of the nucleus of the egg cell as it can make differentiated cells for only things around the organ/tissue its found in. However, the embryonic cell has the capacity to make any cell in the body so as long as its not too differentiated (like in experiment) it will be able to fulfill its role for the egg cell nucleus to create a tadpole
reproductive cloning of mammals: dolly the lamb
dolly the lamb was created by taking the nucleus of mammary glands of an adult finn dorsel ewe and inserting it into an enucleated egg cell of an adult scottish blackface ewe and fusing them together via electrical shocks and inserting it into an adult scottish blackface ewe as the surrogate mother. The result was a phenotypic clone of the adult finn dorsal ewe (white sheep) that created dolly the lamb.
-This shows how the genetic info came from only the mammory gland nucleus which makes sense as it is diploid so it is a clone as it has the genetic information of only the adult finn dorsel ewe.
Carbon Copy
first carbon copy (CC) the cat was made, and she was 100% genetically identical to her mother, but didn’t look exactly the same. This shows that there has to be some distinction or changes that are occurring in development that lead to slightly different presentation that we see
faulty gene regulation in cloned animals due to epigenetic differences
- in most nuclear transplantation studies, many of the embryos don’t develop normally to birth
- many that do survive and are clones have birth defects
- this is bc many epigenetic changes, like acetylation and methylation, in the donor animal has to be undone in nucleus of donor cell and then redone again in clone; very complex process that doesn’t go right all the time, hence defects/not coming to term
Shinya Yamanaka- Induction of Pluripotent stem cells
Shinya Yamanaka created induced pluripotent stem cells that has properties of embryonic cells in the sense that it can create any germ cell. Can go from differentiated embryonic cell or adult cell to undifferentiated and more plastic.
- Did this with mouse embryonic and adult fibroblasts (even tho its embryonic, it was differentiated so no longer pluripotent without IPSC)
- once IPSC is done to the mouse embryonic fibroblasts, it’s morphology is similar to embryonic stem cell, not 100% successful (still some fibroblasts seen) but enough that we can generate the desired germ cell
- very useful technique for therapeutics
