Control of Cell Differentiation Flashcards
what do specialised cells need perform their function?
Specialised cells require specialised structures and specific protein complements in order to perform a specialised function
what are the 3 key processes that cause the development of a human?
These all come from a single zygote through these key processes:
cell division (expansion)
cell death (elimination)
cell differentiation (specialisation)
how many cells and cell types does an adult human have?
An adult human has 10^13 cells in total and around 200 different cell types
what is a stem cell?
a cell type that can differentiate into any type of cell including more stem cells. Early embryos are full of stem cells
what are the 3 steps that differentiation occurs in?
Maintenance: Stem cells self-renew to maintain a sufficient stock
Expansion: Stem cells receive internal/external signal (e.g. hormones) from the environment, informing them of what cell is required
Stem cells then commit & form progenitors- more cell division & differentiation occurs as cells change their pattern of gene expression.
Progenitors can only differentiate into a limited number of cells
Differentiation: cells eventually become terminally differentiated and can only divide into identical cells
define cell potency
a cell’s ability to produce different terminally differentiated cells
Potency decreases as cells commit down differentiation pathways
define pluripotent
The ability to differentiate into any type of terminally differentiated cell
define multipotent
The ability to differentiate into a certain number of terminally differentiate cell
define unipotent
Can’t differentiate and can only produce identical cell
how does blood differentiate (haematopoiesis)?
(include the 2 initial pathways)
The initial stem cell is not pluripotent but haemopoietic – restricted to certain blood cells.
Two initial pathways: oligopotent cells- can only make blood cells
1) myeloid progenitor cell (erythrocyte, platelets, wbc e.g., neutrophil and macrophage)
2) lymphoid progenitor cell (b cell and t cell) pathway
Go through a bunch of progenitors to become a terminally differentiated cell
All WBC look similar because they all come from a common myeloid progenitor
what is the importance of cell differentiation?
For development- Cells specialise to form tissues & organs
Cells need to replicate to replace old/damaged cells
explain how the requirement for cell differentiation is continuous and huge
RBC are constantly being renewed
adult human produces over 1 million mature blood cells a second
production can increase 5- 10 fold in times of need
blood cell homeostasis requires balance between production and destruction
skin is also constantly replaced
what makes cells different from one another?
different patterns of gene expression so have distinct functional roles due to the different proteins they express (e.g. haemoglobin only expressed in erythrocytes)
what are the different features of a cell that are unique/ shared?
proteins defining cell type features are unique to a particular cell
the following may be unique/shared:
metabolic proteins
structural proteins
regulatory proteins
what are the characteristic proteins in erythrocytes?
cell defining proteins e.g. haemoglobin
metabolic proteins e.g. carbonic anhydrase- regulates blood pH
structural proteins e.g. spectrins- form part of the membrane skeleton. allows the membrane to deform and fit through capillaries.
Anion transporter- that is specific to them
regulatory proteins e.g. GATA-1 – transcription factor
what are the proteins that interact with platelets?
involved in homeostasis
collagen receptor- respond to damage of RBC by activating platelets
fibrinogen receptor- involved in blood clotting.
platelets have a receptor for fibrinogen and thrombin
granule proteins
what are housekeeping genes?
constitutive genes required for the maintenance of basic cellular function, they are expressed in all cells under normal conditions e.g. genes that code for proteins such as RNA polymerase, pyruvate kinase, histones etc.
how are genes regulated?
most gene regulation occurs at a transcriptional level (most efficient)
through transcription factors.
what are the two parts of a transcription factor?
Transcription factors are modular – contain two parts
1) DNA-binding domain – recognises and binds to a DNA sequence in promoter/enhancer regions
2) Activation/repression domain – interacts with RNA polymerase to upregulate/downregulate gene expression
what do transcription factors do?
Transcription factors will up-/downregulate different genes resulting in different protein compliments produced
different lineages are expressed
This is why progenitors have the ability to go in different directions – all depends on what transcription factors bind to the DNA
what happens to genes as development occurs?
As development occurs, gene switches take place
E.g. allows for switch between foetal and adult haemoglobin
what is haemaotopeisis?
multipotent primitive cells that can develop into all types of blood cells, including myeloid-lineage and lymphoid-lineage cells
how is the bone marrow specialised for HSC?
bone marrow has a really complex structure
important to haemaotopeisis
The bone marrow niche, which supports self renewal and commitment to differentiation has several components:
- Cellular Components
- Molecular Components
what is the EPO cycle?
1) If I donate blood my low blood volume is detected due to low oxygen in my blood stream
2) There is a detector for oxygen saturation in the proximal tubule (kidney)
3) Once low oxygen has been detected the signal (EPO) is released into the blood stream by the kidneys
4) EPO binds to membrane receptors of haemopoietic stem cells present in the bone marrow.
5) EPO stimulates stem cells to produce RBC progenitors which are then converted into red blood cells
6) RBC carry more oxygen which increase oxygens levels so low oxygen level is switched off
how does the EPO mechanism work?
1) Only haemopoietic stem cells have EPO receptor so only they respond to EPO.
2) EPO binds to a EP receptor on the cell surface membrane
3) Once it binds to the receptor it activates transcription factors which turns on genes
4) This regulates a cascade of protein which bind to other genes
5) This eventually results in the generation of all the required proteins for RBC
explain the clinical implication: deregulated differentiation processes
Problems with differentiation processes resulting in tumour
Mutation occurs at either a stem cell or at progenitor.
This results in a massive accumulation of progenitors (tumour)
- This may be because stem cells over proliferate to produce a lot of progenitors
- Or mutation means progenitors can’t differentiate into terminally differentiated cells.
Example: Leukaemia- tumour is an accumulation of progenitors (blasts). Mutation means progenitors can’t differentiate into terminally differentiated B cells
explain the clinical implication: prospect of “cell based” therapies for some diseases
Prospect of stem cell therapies for disease
Stem cells can be differentiated into specialised cells and tissues for treatment via transplantation
You can also convert fibroblast cells in to muscle cells
Con = immune-rejection - use patient’s own stem cells/somatic cells
You can also convert terminally differentiated cells (fibro blast) back into stem cells
how do you generate an induced pluripotent cell?
by studying pluripotent stem cells, we can now generate “induced pluripotent stem cells” (iPS)
we do this by taking a terminally differentiated cell and introducing 3 key transcription regulators that encode DNA
resulting in your induced pluripotent stem cell that can be differentiated into fat cell, neurone, macrophage etc
why is producing induced pluripotent stem cells (iPS) useful?
useful bc you can take any cell from an individual with a disease, turn it into and iPS and use it to screen drugs and help with understanding genes
