deck_3739186 Flashcards
what are stem cells?
1) Stem cells are capable of producing many types of differentiated cells. 2) These cells are derived from non-specialist (undifferentiated) cells called stem cells3) These cells are specialised to carry out specific functions (differentiated)4) All of capable of self-renewal, but some are able to produce a wider range of cell types than others. 5) Differentiation is (normally) a one way process. Cells cant revert back and become stem cells again and they can’t become another type of cell.
outline the 3 different types of stem cells.
1) Totipotent: Capable of producing any cell type2) Pluripotent: Capable of producing any cell within a major lineage (ectoderm, endoderm, mesoderm)3) Multi-potent: capable of producing a restricted set of related cells
name some tissues with constant turnover and tissues with little or no turnover.
constant turnover:1) haematopoietic system - bone marrow 2) Intestine 3) hair follicle 4) interfollicular epidermis - basal layer of epidermislittle or no turnover:1) brain - subventricular zone, subgranular zone 2) skeletal muscle- between the basement membrane and the muscle fibres
What causes differentiation to occur?
1) Changes in gene expression2) During stem cell differentiation many genes (~1500) change their expression – some increasing and some decreasing.-DNA microarrays allow us to monitor changes in thousands of genes at the same time.3) Genetic factors: Transcription factors bind to specific regions of DNA and turn on specific genes. Repressors bind to specific regions of DNA and inhibit transcription4) Epigenetic factors: - Chromatin remodelling can prevent or enhance transcription. - Methylation of DNA can silence genes- normally adding a functional group to cytosine switches the gene off. in a heart cell all the other genes would be switched off while only the heart cells will become increasingly dimethylated so those specific genes are on.
What triggers changes in gene expression?
1) Signals triggering differentiation-retinoic acid can differentiate a stem cell into a neurone - dibutyryl cAMP, retanoic acid can differentiate steam cells into smooth muscle
Where do differentiation signals come from?
1) The stem cell niche is the environment surrounding the stem cell. It consists of:-Other cells (stromal cells)- Secreted molecules such as growth factors- The extracellular matrix and the physical properties of the environment2) Signals from cells surrounding the stem cell niche maintain stem cells and promote differentiation when required3) These signals can be soluble factors, the extracellular matrix or other cells and they trigger changes in gene expression.
differentiate between environmental and divisional asymmetry.
1) in divisional asymmetry specific cell-fate determinants in the genome or cytoplasm are distributed unequally during cell division. after cell division only one daughter cell receives the determinants thus retaining the hematopoietic stem cell while the other daughter differentiates 2) in environmental asymmetry one haemotopoietic stem cell produces two identical daughter cells initially; However only one remains in the haemotopoietic niche and retains the stem cell identity while the other enters a different environment favouring its differentiation
define: stem cell niche
Stem cell niche refers to a microenvironment where stem cells are found, which interacts with stem cells to regulate cell fate.
describe the stem cell niche of skeletal muscle
1) Skeletal muscle stem cells (satellite cells) occupy a niche on the edge of muscle fibres. 2) They are activated by muscle damage and emerge from their niche onto the surface of the fibre.3) They then move to the site of injury, differentiate into new muscle cells and the remaining stem cell returns to its niche.4) During the differentiation process the cells lose expression of the Pax7 gene and increase expression of the myoD gene.
describe the stem cell niche of hair follicles
1) The human scalp sheds ~50 –100 hairs each day. 2) Stem cells at the base of a hair follicle replace the lost hair3) The stem cell population wraps around the follicle, creating a compartment, called the “bulge.“ which is the stem cell niche.4) The stem cells are multipotent and can regenerate not only lost hair but also sebaceous glands and epidermis.
describe the Stem cell niche in the brain
1) the discovery of neural stem cells with self-renewing capacity and multi-potency has shown that the birth of new neurons continues throughout adulthood. Adult neurogenesis occurs in two primary locations: the olfactory bulb and the central part of the hippocampus.2) In the hippocampus, neural stem cells sit in a layer below their progeny, the granule neurons .3) When activated by extrinsic stimuli, they enter mitosis and generate neuron progenitor cells, which eventually mature into neurons and migrate into the layer above. 4) The number of neural stem cells in the hippocampus decreases over time, possibly contributing to the cognitive impairment associated with ageing
Is differentiation always a one way process?
1) De-differentiation can occur in nature, for example as part of a regenerative process in amphibians and worms.2) De-differentiation can occur in cancer, with cancer cells acquiring stem cell like properties.-Dedifferentiation, is a cellular process often seen in more basal life forms such as worms and amphibians in which a partially or terminally differentiated cell reverts to an earlier developmental stage, usually as part of a regenerative process.
Can we induce de-differentiation to produce stem cells from differentiated cells?
1) The nuclei of differentiated cells can be reprogrammed with the right signals2) Differentiation can be reversed through the addition of four signals to produce induced pluripotent stem cells3) Some of these signals have now been identified. The addition of four factors – called Oct4, Myc, Sox2 and Klf2 – can reprogram differentiated cells and turn them into stem cells capable of producing all the cells in an organism4) These iPS cells can then be turned into new cells types by adding the right signals
what are Induced pluripotent stem cells?
1) iPS cells are a type of pluripotent stem cell that can be generated directly from adult cells2) These iPS cells can then be turned into new cells types by adding the right signals3) e.g. Differentiated human skin fibroblasts were induced to form pluripotent stem cells. They were then treated with signals that induced differentiation into cardiomyocytes (heart cells). Twelve days after induction clumps of cells started beating.
what are neurospheres? and why are they of great interest to scientists.
1) When cultured with growth factors in vitro, neural stem cells can generate neurons , as well as the cells that support them— astrocytes and oligodendrocytes. 2) In culture, neural stem cells group together in ball-like clusters, called neurospheres 3) Neurospheres are of great therapeutic interest because they have the potential to regenerate and replace neurons lost in traumatic brain injury and neurodegenerative diseases, such as Parkinson’s disease, Alzheimer’s disease, and multiple sclerosis.
