cell differentiation Flashcards
cell differentiation
process through which a cell undergoes changes in gene expression & gene activity to specialise & take on specific roles in an orgnaism.
cell lineage
series of successive cell types = from the zygote to a particular mature cell type
ES cell
embryonic stem cell; able to differentiate to any cell type
gene expression
synthesis of the product of a given gene; a protein/ functional RNAs like tRNA.
Involved transcription & for proteins translation.
household gene
gene expressed in nearly all cell types e.g. tubulin
luxury gene
gene expressed in only one or a few cell types
master gene regulator
TF that coordinately regulates many or all of the genes speifically expressed in a particular cell type
modulation (of gene expression)
a simple,reversible change in gene expression with no change to cell type
pluripotent
able to produce several functional cell types.
also used for ESCs that can produce cell types of all 3 germ layers
pioneer factors
TFs that can bind to condensed chromatin, remodel it and initiate cell fate and differentiation (master regulators e.g ; SOX2, OCT4, NANOG)
postnatal/ adult SCs
immature cell that can both divide to produce further cells like itself & differentiate to replace functional cells that are worn out or lost
precursor/progenitor cells
any immature cell type able to differentiate to other cell type/s
promoter
a stretch of DNA at the 5’end of a structural gene which regulates transcription of that gene by binding to certain TFs (proteins that regulate transcription)
terminal differentiation
production of a mature functional cell type that can’t divide e.g. neurons, skeletal, muscle, granulocytes
totipotent
able to produce all cell types of both body + extra embryonic parts e.g. placenta, membranes)
cell determination
process whereby cell fates becomes stable. followed by cell differentiation. when a cell chooses a particualr ‘fate’ it’s said to be ‘determined’.
implies stable change.
what is the endpoint of cell differentation?
wide variety of specialised cells
what happens to dividing cells as we age?
decrease
division of cells during cell determination
asymmetrical cell division due to differential distribution of cytoplasmic molecules (proteins or mRNAs) within a cell before it divides
- 2 daughter cells > different fates> different gene expression profile
what causes cell determination?
- inductive signals from neighbouring cells is most common cause
- one group of cells influences development of another
embryonic stem cells; totipotent or pluripotent SCs
- derived from 4 or 5 day old human embryos in human blastocyst phase of development
germ layers are made from what SCs?
totipotent ESCs that produce pluripotent ESCs that go on to differentiate into the endoderm, mesoderm and ectoderm
adult stem cells
- multipotent
- give rise to various types of cells in the tissues they are in; tissue specific
- function; cell turnover
- low in tissues where low rate of cell turnover e,g. brain
what are stem cell niches?
microenvironments where tissue specific stem cells are maintained
what do these niches help to maintain?
- secreted soluble signalling factors; GFs and cytokines
- physical parameters; shear stress, tissue stiffness and topography
-environmental signals; metabolites, hypoxia, inflammation
haematopoietic stem cells (HSCs)
multipotent stem cells anchored to fibroblast-like osteoblasts of the marrow of long bones.
produce all blood cells & some immune system cells.
regular self-renewal
mesenchymal stem cells (MSCs)
stromal cells found in bone marrow & other organs
poorly defined and heterogenous
don’t self renew very regularly but are multipotent
dont give rise to cartilage (chondrocytes), bone (osteoblasts), muscle cells (myocytes) and adipocytes.
oligopotent stem cells
can differentiate into only a few cells and include myeblast stem cells that produce 3 types of WBCs; eosinophils, neutrophils, basophils
what differentiates a skeletal muscle cell?
- muscle actin
- a-actinin
- muscle myosin
- muscle creatine kinase
- myoglobin
what differentiates a melanocyte?
- tyrosinase
- dopachrome tautomerase
- myosin 5 a
- melanocortin-1-receptor
what do Klf4 and c-MYC do in ESCs?
cooperative factors that are highly expressed in ESCs and help maintain their pluripotency.
function of cooperative factors
direct conversion of cell fate between differentiated cell states
e.g. fibroblasts + GATA4 = cardiomyocyes
somatic cell nuclear transferase (SCNT)
artifical removal of uclear of a differntiated somatic cell & its placement in a denucleated egg cell
what happens and what are the limitations?
- introduced nucleus is reprogrammed by factors in egg cytoplasm
- new egg behaves like a zygote (totipotent)
- challenging and time consuming
induced pluripotent stem cells (iPSCs)
- pluroporent cells artificially produced from somatic cells
- epigenetically reprogrammed into PSCs
- can potentially produce almost all cells of the organism
what is added to adult fibroblast cells to make them iPSCs?
yamanka’s cocktail
what is in yamanka’s cocktail?
Oct3/4, SOX2, Klf4, c-MYC , NANOG, LIN28, Glis1
OCT4 and Velychko et al.
often considered the most important factor in the mix show that although we know underexpression or removal of Oct4 = lack of differentiation, overexpression = epigenetic changes and deterioration in quality of iPSCs
examples of iPSCs
- cardiomyocytes
- adipocytes
- neural cells
- pancreactic b-cells
function/ use of iPSCs
- gene therapy
- regen.medicine / cell transplantation
- model disease & drug screening
