Cell Differentiation And Gene Expression Flashcards
Define cell differentiation
The process through which a cell undergoes changes in gene expression and gene activity to specialise and take on different roles in an organism
Is cell differentiation reversible?
No
What happens to the proportions of dividing cells when humans approach maturity
It falls
Define stem cells
Undifferentiated and unspecialised cells of the human body
What is a totipotent cell (with an example)?
Able to differentiate into every cell type in the body - zygote
What is a pluripotent cell (with an example)?
Able to differentiate into most, but not all cells (ie not placenta) - embryonic cells/ blastocyst
What is a multipotent cell (with an example)?
Can differentiate into a limited number of cells - hematopoietic and mesenchymal cells
What is a unipotent cell (with an example)?
Can only form one type of cell - sperm cells and dermocytes
What is the asymmetric division theory of how a stem cell divides and what does it produce?
A fate regulator (polarity protein) distributes unequally in the daughter cells - produces one differentiated cell and one stem cell
What is the symmetric division theory of how a stem cell divides and what does it produce?
Some cells may divide to give identical daughter stem cells while other stem cells divide to generate two progenitor cells committed to differentiation- two differentiated cells or two stem cells
Where do embryonic stem cells come from?
A four or five day old human in the blastocyst phase of development.
Why aren’t embryonic stem cells sometimes considered stem cells?
They differentiate into specialised cells so quickly
What type of stem cells are embryonic stem cells?
Pluripotent
What type of stem cells are adult stem cells?
Multipotent
What is a tissue specific cell?
A cell that can give rise to types of differentiated cells within the tissue they reside in
What is the function of adult stem cells?
To replace dead cells
What are the levels of adult stem cells like?
In low rate of cell turnover tissues (like brain) it is low and in high turnover rate tissues (like blood) it is high
What is a stem cell niche?
A special supportive micro-environment where tissue specific stem cells are maintained
What are stem cell niches influenced by?
Neighbouring niche cells, secreted soluble signalling factors, physical parameters and environmental signals
What are the main factors in stem cell niches?
- secreted factors
- inflammation and scarring
- extracellular matrix
- physical factors
- hypoxia and metabolism
- cellular components
Where do blood cells come from (dependant on the maturity of the human)
Made in embryonic structures until week 20 when they originate from the bone marrow
What is a hematopoietic stem cell?
Multipotent stem cells anchored to fibroblast-like osteoblasts or the marrow of long bones
What do hematopoietic stem cells produce?
All blood cells and some immune system cells
What are mesenchymal stem cells?
Stromatolites cells found in bone marrow and other organs. They’re poorly defined and heterogenous.
Do mesenchymal stem cells self renew?
No
What do mesenchymal stem cells produce?
Chondryocyctes, osteoblasts, myocytes and adipocytes
What is a chondrocyte?
Cartilage cell
What is an osteoblast?
Bone cell
What is a myocyte?
Muscle cells
What are progenitors?
Oligopotent cells only found in the myeloid or lymphoid lineage
Can progenitors replicate indefinitely?
No, only a limited number of times
What helps to determine how a cell differentiates?
The type and number of proteins
What allows the analysation of the transcription profile of each cell?
RNA sequencing and microassays
How do TFs affect gene expression?
They bind to regulatory regions of genes and affect its expression by switching it on or off
Where are the two places TFs can be?
Differentiation of stem cells and some are tissue specific
What is a basal transcriptions factor?
A TF necessary for the RNA polymerase to function at the site of transcription in eukaryotes
What is considered the most basic set of proteins needed to activate a gene for expression?
Basal TFs
Where do basal TFs bind to activate transcription?
The 5’ region of DNA
How do specific TFs differentials regulate the expression of various genes?
By binding to the adhesive regions of DNA or the promoter regions
What do specific TFs ensure?
The genes are expressed in the right cell at the right time in the right amount
How do the different TFs know which genes to bind to?
The binding elements (motifs) in their promoters and enhancers
What is a housekeeping gene?
Transcribed in all or nearly all cell types
What is a luxury gene?
The specialised genes expressed in only some types of cells
What is a pioneer factor?
TFs that can bind to condensed/ closed chromatin, remodel and initiate cell fate and differentiation
What does a master regulator do?
Control the differentiation of the cell
How common are pioneer factors in embryonic stem cells (and why)?
Very - needed to maintain their pluripotency
Is DNA methylation heritable and reversible?
Yes
What does DNA methylation result from?
External or environmental factors as part of the development programme
Describe what DNA methylation does (and what it results in)
Covalent addition of the methyl group at the 5-Carbon of the cytosine ring resulting in 5-methyl-cytosine (5-mC)
Where does 5-mc occur in somatic cells?
CpG sites
Where does 5-mc occur in embryonic stem cells?
Can happen anywhere
What is a CpG site?
A place where a cytosine is next to a guanine
What does a de-novo methyltransferase do?
Methylate CpG pairs during differentiation
What does a maintenance methyltransferase do?
Methylates the opposite strand
What are the consequences of DNA methylation?
-methylation could increase folding and silencing
In embryonic stem cells are the majority of CpG sites methylated?
Yes
Where are globin genes expressed and what happens when they aren’t?
Red blood cell lineages- they’re methylated in all other cell types
Give the steps of somatic cell nuclear transfer (SCNT)
- remove nucleus from a differentiated somatic cell and place it in a denucleated egg cell
- new nucleus is reprogrammed by factors in the egg cytoplasm
- the new egg behaves like a zygote (totipotent)
What is an induced pluripotent stem cell (iPSc)?
Pluripotent stem cells artificially produced from somatic cells
What is yamanakas cocktail and when is it used?
The four transcription factors iPScs are exposed to
What are iPScs used for?
Gene therapy
Model disease and drug screening
Regenerative medicine/ cell transplantation