Differentiation and Gene Expression Flashcards
What is cell differentiation?
Cell differentiation is the process through which a cell undergoes changes in gene expression and gene activity to specialise and take on specific roles in in an organism
`the endpoint is a wide variety of specialised cell types
This process is irreversible (for the most part)
What are the categories that cells usually fall into when it comes to cell division?
Proportion of dividing cells falls as we approach to maturity
In adults:
Majority of the cells are terminally differentiated (they cannot divide)
A small minority are capable of cell division:
Some actively dividing
Some quiescent and divide only occasionally
What are stem cells?
Definition: undifferentiated and unspecialised cells of the human body
Found in embryos (embryonic stem cells) and in adults (adult stem cells)
Able to differentiate into many cells of an organism and have the ability to renew themselves by cell division
What are the two theories as to how stem cells divide?
Asymmetric division-a stem cell produces one differentiated cell and one stem cell
A fate regulator (e.g. polarity protein) distributes unequally in the daughter cells.
Symmetric division- a stem cell produces two differentiated cells or two stem cells
Some cells may divide to give identical daughter stem cells while other stem cells divide to generate two progenitor cells committed to differentiation
What is the potential of embryonic stem cells?
Totipotent or pluripotent (but in exam its pluripotent)
Totipotent cells can differentiate into any embryonic and extra-embryonic cells
The only totipotent cell is the zygote
Pluripotent cells of the embryo have been shown to be transiently existing cells, not stem cells
Derived from a four- or five- day-old human embryo in the blastocyst phase of development
What are the different types of stem cells and their potential?
Multipotent:
Typically give rise to various types of differentiated cells within the tissue they reside in e.g. hematopoietic stem cells and mesenchymal stem cells
Tissue-specific stem cells:
Their function: dead cells replacement (cell turnover)
Low number in tissues where low rate of cell turnover (adult brain) and abundant in tissues such as intestine epithelium and blood cells
Unipotent stem cells can form one type of differentiated cell only e.g. spermatogonial stem cells and dermatocytes (NOT adult stem cells)
How are tissue-specific stem cells maintained
Tissue-specific stem cells are maintained in special supportive microenvironments called stem cell niches
Supporting ECM, neighbouring niche cells, secreted soluble signalling factors (such as growth factors and cytokines), physical parameters such as shear stress, tissue stiffness and topography), and environmental signals (metabolites, hypoxia, inflammation)
What are some examples of stem cells?
Blood cells initially made in certain embryonic structures
From foetal week 20 onward they originate from the bone marrow
Hematopoietic stem cells (HSCs): multipotent stem cells anchored to fibroblast-like osteoblasts of the marrow of long bones
Produce all blood cells and some immune system cells
Regular self-renewal
Mesenchymal stem cells (MSCs): stromal cells found in bone marrow and other organs
Poorly defined and heterogeneous
They do not self-renew very regularly but they are multi-potent
Give rise to cartilage (chondrocytes), bone (osteoblasts) and muscle cells (myocytes) and adipocytes.
What are progenitor cells?
Progenitor cell is a stem cell that has a tendency to differentiate into just one specific type of cell- only one lineage and therefore are called oligopotent
Can divide only a limited number of times
How is gene differentiation regulated?
Cells differentiate through differential gene expression
The types and number of proteins a cell generates help to determine how a cell differentiates
How can we analyse the transcription profile of a cell?
RNA sequencing and microarrays assays allow analysing of the transcription profile of each cell
How do transcription factors work generally and what are the two types of transcription factors?
Some genes need to be switched off and others switched on- done by transcription factors Transcription factors (TF) bind to regulatory regions of a gene and affect its expression by switching it on/off Certain TFs are tissue-specific and different TFs are associated with differentiation of stem cells into different tissues Different genes are activated by different TFs, according to the binding elements (motifs) in their promoters and enhancers Each cell type transcribes a different set of genes Some genes are transcribed in all or nearly all cell types and are called house-keeping genes (e.g. basic metabolic enzymes) The specialised genes expressed in only some types of cells are called luxury genes (haemoglobin gene in red blood cells)
What are pioneer factors? What do they do?
Transcription factors that can bind condensed/close chromatin, remodel it (open it and close it) and initiate cell-fate and differentiation (master regulators) e.g. OCT4, BMP4, SOX2 and NANOG
Highly expressed in embryonic stem cells and needed to maintain their pluripotency
Can activate or inhibit gene expression through:
A) Histone modification
B) DNA methylation blockage
What are epigenetics?
Heritable and reversible changes in gene expression which do not involve a change in the DNA sequence
Results from external or environmental factors or, as part of development program
Epigenetic mechanism that occurs by the addition of a methyl (CH3) group to DNA
How does DNA methylation occur?
Covalent addition of the methyl group at the 5-carbon of the cytosine ring resulting in 5-methylcytosine (5-mC)(- this is a mono-methylation)
In somatic cells, 5-mC occurs on CpG sites (cytosine nucleotide is located next a guanidine nucleotide) Exception: embryonic stem cells, where is also present in non-CpG regions
Methylation pattern is ‘remembered’ in daughter cells
During differentiation unmethylated CpG pairs can become methylated by a de novo methyltransferase
Copied to opposite strand (also CpG) by a maintenance methyltransferase
Methylation of a gene (especially its promoter or control sequence) increase folding (heterochromatin) and silencing transcription
In embryonic stem cells the majority of CpG sites are unmethylated
Globin genes are expressed in the red blood cell lineage, but not elsewhere
Their promoters are methylated in other cell types
In sperm, most genes are silenced by methylation
DNA is very heterochromatic
