L4 Differentiation Flashcards
What makes cells different from each other?
Changes in gene expression underliw the diversity of cll types in the body.
What does cell diversity primarily result from?
Cell diversity primarily results from differences in gene expression
All cells have the same gene content ….?
All cells have the same gene content, but different sets of proteins
What does terminally differentiated state mean?
Refers to the final stage of cellular differentiation. They are dedicated to performing their specific roles within the organism
What do cells change their expression profile in response to?
Cells change their expression profile in response to signals and other cues in the environment
Do cells express a fraction of their gene?
Yes
In what state do cells often express different genes?
In a disease state.
What do stages of differentiation correlate with?
It correlates with stepwise expression of different regulatory transcription factors
What are the 5 stages of potency within cells?
- Totipotent
- Pluripotent
- Multipotent
- Bipotent
- Unipotent
What is the highest level of potency?
Totipotent. A totipotent cell can differentiate into any cell type.
What is differential gene expression?
If different cells have differences in gene expression it is called differential gene expression.
Does the level of transcription affect the level of expression?
Yes, increasing the level of transcription tends to increase the expression of a gene
What does transcriptome mean?
All the genes that are actively being transcribed.
Complete set of RNA transcripts produced by the genome of an organism
What is proteome?
Complete set of proteins expressed by a genome
What do DNA binding proteins bind to?
DNA binding proteins bind to the DNA backbone and reach into the major groove to form very specific bonds.
What are the other names for a binding site?
- Cis acting element
- Regulatory element
- Enhancer
- Silencer
What is a binding site?
A binding site is a stretch of DNA with a sequence that is recognised and bound by the transcription factor. The bonds are H - bonds and are not stable
Silencers are the binding site for what?
They are the binding site for transcriptional repressors
What are enhancers?
They are a binding site for transcriptional activators.
Give me examples of inputs that can be referred to as a genetic switch
Strongly activating assembly, strongly inhibiting protein, spacer DNA, weakly activating protein assembly
Each switch is responding to extrinsic or instrinsic regulation
What is an expression profile?
It essentially provides a snapshot of which genes are actively being transcribed in a cell or tissue at a particular time
Can a single transcription factor create an expression profile ?
Yes
Are enhancers promiscuous?
Yes, they will work on any gene
How do trancriptional factors bind?
They bind in clusters.
What does “Enhancer are promiscuous” mean?
This means that they will work on any gene.
Are transcriptional factor specific to a single gene?
No they are diverse in selection of gene.
In summary, what is transcription factor activity dependent on? (3)
Extrinsic signals
Intrinsic factors
Regulatory binding sites
Give me 4 examples of muscle specific proteins
Muscle - specific actin
Myosin II
Tropomyosin
- Muscle-specific enzymes (e.g. creating phosphate kinase)
What is MyoD? (Check)
Gene and transcription factor
What does transfect mean?
Transfect = introduce a modified gene into cells or an animal (to make a transgene)
Give me some features of MyoD
- Transcription factor
- Expressed only in muscle precursors and muscle cells
- Controls expression of genes for muscle differentiation
- Maintains its own expression
What was the experiment used to find out whether MyoD is sufficient for muscle cell differentiation?
Experiment: transfect fibroblasts with activated MyoD gene
What was the result and conclusion for the sufficiency experiment?
Result: fibroblasts now differentiate into muscle
Conclusion: MyoD is sufficient to direct muscle cell fate in fibroblasts
Define differentiation?
Differentiation is a multi-step process that involves extrinsic cues and the sequential expression of different transcription factors.
Do fibroblasts normally express MyoD or other specific proteins?
No, fibroblasts do not normally express them
What are the three steps in muscle cell differentiation?
- Determination
- Differentiation
- Maturation
If a mice lacking both MyoD and Myf5 genes, what affects does this have?
Mice will lack all skeletal muscles, so both genes do have an important role in muscle differentiation
What’s the difference between genes being sufficient or necessary/ required?
A gene is required for a particular process or outcome of that process cannot occur without the gene’s presence
A gene is sufficient for a particular process or outcome if its presence alone is enough to cause that process to occur
In the embryo where does most muscle cells comes from?
They come from somites.
In adults where does muscle cells come from?
In the adult, muscle cells are renewed by satellite stem cells that line muscle fibres
Explain how blood cells are another classic model for differentiation
1; in the mammalian embryo M blood cells are first made in the yolk sac and then the live. In adults, blood is made in the bone marrow.
As cells travel toward terminal differentiation, they express different sets of transcription factors