Lecture 4 - Differentiation Flashcards
What is the name given to the state of a cell once it’s final fate has been determined?
Terminally differentiated state
What causes cells to change their expression profile?
Signals & other cues in the environment (regulated by signals)
Describe the stepwise restriction in potency
Totipotent
Pluripotent
Multipotent
Bipotent
Unipotent
Describe totipotency
Can become any cell in body (embryonic stem cell)
Describe pluripotency
Can make most cell types (term layer after gastrulation)
Describe multipotency
Can make all cells within a tissue
Describe bipotency
2 cell types
Describe unipotency
1 cell type - may produce stem cells through
What changes in different stages of differentiation?
The expression of regulatory transcription factors changes
What do researchers use to track different stages of differentiation?
Gene (markers)
What is the term given to a differences in gene expression?
Differential gene expression
What are other names for a binding site?
- cis acting element
- regulatory element
- enhancer
- silencer
Why is binding between a transcription factor and a binding site in the DNA only a temporary event?
Hydrogen bonds are weak
What is an enhancer?
Binding site for transcriptional activators (and repressors)
What is a silencer?
Binding site for transcriptional repressor
What are genetic switches?
Regulatory transcription factors modulate the level of expression of many genes - can activate some genes and inhibit others - have huge effect on cell fate.
- (basically inputs that alter gene expression)
What are examples of genetic switches?
- strongly activating assembly
- strongly inhibiting protein
- spacer DNA
- weak activating protein assembly
What does the genetic switches respond to?
Intrinsic & extrinsic regulation
What regulates gene activity on a larger scale?
Feedback loops - activation of one gene leads to multiple genes being activated
What does transcription factor activity depend on?
- extrinsic signals
- intrinsic signals
- regulatory binding sites
- accessibility of chromatin
What 4 muscle-specific proteins are required for a somite to turn into a terminally differentiated muscle?
- muscle-specific actin
- myosin II
- tropomyosin
- muscle-specific enzymes (e.g. creatine phosphate kinase)
What is MyoD?
transcriptional factor expressed only in muscle precursors & muscle cells. It controls expressions of genes for muscle differentiation and maintains its own expression.
Fibroblasts were transfected with MyoD gene. The fibroblasts now differentiated into muscle. What does this suggest?
MyoD gene is sufficient to direct muscle cell fate in fibroblasts.
Mice without MyoD develop with normal skeletal muscle. What does this suggest?
MyoD is NOT required for muscle cell differentiation
What is another gene that acts redundantly with MyoD?
Myf5
What occurs if a mice lacks both MyoD & Myf5?
they lack all skeletal muscle, so both genes do have an important role in muscle differentiation.
Is differentiation a single-step process?
No - differentiation is a multiple-step process that involves many external inputs.
Where does the muscle come from in the embryo?
The somites
What are muscle cells renewed by in adult cells?
Satellite stem cells renew muscle cells that line muscle fibres
Describe the potency of haemopoetic stem cells
Multipotent (can also create itself)
Where are blood cells made in the mammalian embryo?
In the yolk sac & then liver
Where are blood cells made in adults?
Bone marrow
