Lecture 26 (cellular differentiation, stem cells and modern medicine) Flashcards
Cells become more specialised and less flexible during development … explain
Embryo begins as a small number of naive, totipotent cells (have the total potential to go on and make every single cell type plus placenta contribution)
Embryonic stem cells (cells in the middle) can give rise to all cell types except trophectoderm (pluripotent)
Progressive restriction of cell fate until terminally differentiated (stays in that role for the rest of its life) , and can only give rise to the same type of cell. Exception - stem cells, germ cells (remain totipotent to give rise to the next generation)
If every cell went on to become a differentiated cell then if cells were damaged/out of business we wouldn’t be able to replace them.
Doesn’t matter what embryo you look at, cells are going to divide, move around and then they are going to start specialising into different roles
8 cell stage to blastocyst
8 cell stage
- twins form when there is 2 balls of 4 cells
- Cells are very identical and start off doing the same thing
Cell polarisation
- Cells attach to each other
- Polarise means they have an inside and outside and make microvilli on the outside
Compaction
-Cells are tightly packed together
Inner, apolar cells cut off
-Inner cells are cut off from the intrauterine environment and the outer ones are still in contact with this environment
Blastocyst
-ICM (formally apolar) and have the potential to make the 200 different cell types that make up you
Outside cells from previous step after a few more cell divisions terns into the outer layer which is called the trophectoderm, the embryos contribution to the placenta, this part is unable to contribute to the embryo structures
Totipotent
Describing a cell that can give rise to all parts of the embryo and adult, as well as extraembryonic membranes (i.e placenta) in species that have them.
Multipotent
Stem cells that give rise to both stem cells and cells that will differentiate into one or more (but not all) types of functional tissue cells. Examples of multipotent stem cells would be adult stem cells such as those from blood (haematopoietic stem cells) or bone marrow.
Pluripotent
Describing a cell (immature cell or stem cell) capable of generating all the cells of an embryo, with the exception of the placenta.
Since all cells have the same DNA, how do cells become specialised?
There are a group of proteins made from genes in our nucleus which are capable of turning on and off other genes, these are called transcription factors or master regulatory genes
Embryonic cells are not differentiated, explain how they become differentiated….
When it is an embryonic cell, at this stage in development the cell could become any type of differentiated cell (it is pluripotent). Genes for specific functions/structures are not being transcribed. For example muscle specific genes are not being transcribed since this embryonic cell is not a muscle cell (it doesn’t need the proteins a muscle needs as it is an embryonic cell)
This cell now must develop into a differentiated cell e.g. muscle cell. The cell is determined because it is set on its path but it is not differentiated yet as it still looks the same. Certain control genes which code for transcription factors become activated.
Finally, the cell is terminally differentiated, playing a functional role in the organism. Transcription factors turn on specific genes for specific cell proteins, sometimes leads to a different transcription factor being differentiated. In the end, proteins specific to the differentiated cell are produced!
Genomic equivalence
Differentiated cells contain all the DNA required to build an entire new organism
The idea that every cell in our body has a complete copy of our DNA. Specialised cells do not throw away the other DNA, however it is very difficult to wake it up and get and make it become an embryonic cell again.
John Gurdon’s frog experiment
Two different tests -
First a less differentiated cells from a frog embryo is inserted into an enucleated egg cell (DNA inside the nucleus is killed with UV light but the cell overall is fine). Now have a diploid nucleus within an empty egg and this keeps developing and becomes an embryo and then a tadpole and then a frog. Most develop into tadpoles and this tells us that all of the nuclei in the frog embryo have the information to make a whole organism. This should not be surprising as the nucleus has come from a 4 cell embryo.
Second test was taking the nucleus from a fully differentiated (intestinal) cell and inserting in into an enucleated egg cell. Even though it is a differentiated cell nucleus, it can still drive the development of a complete frog which tells us that no DNA has been lost (it is just shut away). The other DNA is woken up by putting it into an egg. Most stop developing before the tadpole stage. The fact that most of these experiments fail is because it is hard to wake DNA up and make it go back in time and get rid of all the transcription factors that have tuck themselves in places and formed feedback loops, all of this has to be broken to get the cell back to its undifferentiated state.
Embryonic stem cells
Embryonic stem cells (ESCs) are stem cells derived from the undifferentiated inner mass cells of a human embryo.
These are “harvested” from the inner cell mass (future embryo) of mammalian cells
Human embryonic stem cells are pluripotent; they can develop into any of the 200 or so types of cell in our bodies, given the right conditions
The cells derived from these ESCs are genetically identical to the embryo donor
Induced Pluripotent Stem (iPS) Cells
Induced Pluripotent Stem Cells (iPS) are derived from skin or blood cells that have been reprogrammed back into an embryonic-like pluripotent state that enables the development of an unlimited source of any type of human cell needed for therapeutic purposes.
The technique currently involves genetic engineering, but could be used in therapy in the future
iPS cells can be made from anyone, and are genetically identical to the source skin cells. As they are also pluripotent, they can generate any cell type
Adult (Tissue) Stem Cells
Stem cells can divide without limit (stem cells in your tissue that renew and keep dividing until you die, and if they stop dividing then you die)
Undifferentiated (job is to provide new cells for tissues), multipotent (cant make all cell types) cells
They can divide to give rise to both stem cells and cells which go on to differentiate into one or more (but not all) types of functional tissue cells
Umbilical Cord Stem Cells
Cord blood banking is now a common practice in some countries
Stem cells from blood isolated from the umbilical cord of newborn babies are kept frozen (banked)
The stems cells are multipoint, as they are immature blood stem cells. They are less restricted than blood stem cells from adults.
Can be used to treat leukaemia and many other blood diseases
Adult Stem Cells - renewal tissues
Stem cells are important for tissues such as blood and skin which need constant renewing
Blood stem cells or haematopoitic stem cells are found in the bone marrow and can be used for transplants.
Stem cells can divide asymmetrically, rather than giving rise to 2 identical daughter cells it can produce a stem cell (which goes back into the pool and can keep making stem cells) or progenitor cells which can differentiate into different types. If running low on stem cells, it is also able to divide into two stem cells. If it splits into two progenitor cells then that stem cell is gone from the population forever. Therefore it is important to have a balance between stem cells and progenitor cells.
Adult and embryonic stem cells
A fertilised egg is totipotent, able to give rise to all cell types via cell division
Embryonic stem cells are pluripotent and can become all/any cells of the body
Adult stem cells such as bone marrow cells usually only give rise to one or a few cell types: multipotent
Different culture conditions are used to persuade stem cells to develop into different kinds of differentiated cells
