lecture 6- adult stem cells Flashcards
(26 cards)
what does reprogramming mean
forcing a cell to return to the progenitor state
what is transdifferentiation
when a cell can directly transform into another without reverting back to its progenitor state
what are adult stem cells
a stem cell present in adult tissues that retains the characteristics of stem cells except they are usually uni or multipotent
what are adult stem cells essential for in humans
homeostasis
describe asymmetrical division that occur in adult stem cells
divide into ASC and progenitor/differentiated cell
this occurs 80% of the time
10% is both progenitor
10% is both ASC
what is the physical adult stem cell niche
cell adhesion and extracellular matrix
what is the chemical adult stem cell niche
secreted proteins from cells around the niche and
metabolic interactions (eg. pH)
what are the 3 mechanisms to regulate adult stem cells
epigenetic=histones/methylation influence expression of genes
transcriptional= TFs regulate stem cell proliferation and differentiation
cytoplasmic= asymmetric distribution of proteins govern mode of cell division
where are ovarian germline stem cells found and what are they in close contact with
germanium
close contact with cap cells
how do cap cells control differentiation in drosophila
1)produce TGFb ligands
2)these activate BMP signalling
3)BMP signalling represses bam(which is required for differentiation)
what does reduced dpp/increased bam lead to
GSC differentiation
what does increased dpp/decreased bam lead to
germline tumours
how does the ECM composition affect the stem cell differentiation of ovarian germline stem cells
ECM molecules restrict TGFb ligand diffusion which will allow the cell to differentiate
describe BMP signalling in ovarian germline stem cells
Cap cells release Dpp
Dpp binds to BMP receptors (Tkv/Sax + Punt) on the surface of the GSC.
This triggers phosphorylation of Mad (a Drosophila R-Smad).
pMad binds with Med (a co-Smad) and the complex translocates into the nucleus.
In the nucleus, the complex *represses the expression of the differentiation gene bam , which is critical for initiating differentiation.
As long as bam is repressed, the GSC remains undifferentiated and self-renewing.
High BMP signaling induces Dad, a negative regulator that inhibits the pathway, ensuring signaling doesn’t spread too far from the niche.
what are skeletal muscle stem cells (satalite cells ) activated by
exercise
injury
describe the asymmetrical division of skeletal muscle stem cells
Par 3 present in apical side of cell
Par 1b present in basal side of cell
they anatagonise eachother
par3 -> p38 MAPK -> myogenic cell so differentiates with myoD
par1 -> self renewal with pax 7 gene
how do you get the Par1/ Par3 niche in satalite cells
from the basal lamina
contains laminin which is a ligand for integrin and dystroglycan receptors in SCs and in fibres
what is the basal lamina
a supramolecular structure that anchors to the cell surface via laminin receptors
how does remodelling of the basal lamina support asymmetic cell division
1) when injured, MMP2/9 proteins degrade the local extracellular matrix
2) stem cells actively transcribe and produce a new type of laminin (alpha1)
3) at the same time, it produces a new receptor for this laminin
4) the combination of this initiates Par1 at laminin alpha1 (away from sarcolemma) and Par3 at the side closest to sarcolemma
what are the advantages of adult stem cells
already specialised
no immune rejection
no ethical controversy
what are the disadvantages of adult stem cells
small amounts so you need to amplify
when you remove their niche, they lose capacity
can have genetic damage
what does Conrads epigenetic landscape show
ball = developing cell.
valleys = different cell fates
landscape is shaped by gene regulation, epigenetic modifications, and environmental inputs.
As a cell “rolls” down the landscape, it makes irreversible choices
This illustrates how cells become progressively more committed
The shape of the landscape is determined by epigenetic factors
These factors guide and constrain development.
Early in development, the ball is near the top — the cell is pluripotent and can become many things.
As it moves down, its potential becomes more restricted — reflecting differentiation.
With effort (e.g., transcription factor overexpression), you can push the ball back up the hill or into another valley — like in induced pluripotent stem cells (iPSCs).
what are the 2 ways a cell can revert back to progenitor state
reprogramming
transdifferentiation
how is a stem cell niche determined
combination of local environmental cues and cellular interactions
