November 5, 20110:41 AM
We talked about how adult structures can
Now we talk about how its maintained.
All structures need maintenace. Once cells in
tissues are born they continuously
regenerate. Can happen in 2 level.s
Moelcular turnover: cells stay intact and
molecules in the cells turn over.
Cellular tunroner: cells dies and maintain the
overall tissue structure
The reason that these tissues are maintained
themselves for a lifetime because tehey have
a very specific architectutre and function.
turns into neuro impulses.real speicifc
architecture to detect photons and
convert them into neural impulses the
brain and we all can see.
The brain can convert it to images we can
There is a structure of the cell which has
outer and inner segmens. The disk of
photoreceptor membranes where
photons are detected. This leads to the
change in thec ell --> activation of the
synaptic regions so the single can be sent
to the brain.
If you look at the overall retina, the
photoreceptors are ar ewat the back of
the retins so the light coming it towards
the eye tp the retina, the receptor cells are
in the nack, the neurins and azons are in
front of the receptors . Lights hit the
photoreceptors --> hits the neurons -->
sends signal.this is a specail architecture
in animals. Are the molecule truning over.
The question is are the molecules turning
vier or permant.
BIO230 Page 4 You can use the pulse chhase to look at
moelcaular tunrover. You add a smal
amount pf pulse for a small amount of
time and stop adding it and watch what
happens to is, follow it. Here the
radiolabeled Leucine: AA.we are labelling
all the proteins. Cells will take up the
labelled leucine: ncorpaotaing them to the
newly synthesized protiens in a short
period if time.
1. They are going to be detected in the
cells for an entire life time. Which
means that the same proteins that are
been made which took that protein
stays in the cell for the rest of the life
time of that cell.
2. Or its gradually loses the detection
indicating Moelcular turnover.
1. Time point one: Shortly after leucine was added. The labelled proteins are found in the nucleus. Where the proteins
are made and labelled. Fter the pulse of the other leucines are been made.
2. The proteins are made in the nucleus. So there are other leucines which are been made and they move up into the
mmebranes and then they differ into the pigmented epithelium cells. They keep on shifting up and insert the
pigmented epithelium in the photorecptors. One thing is that there isa flow of molecules…there are constant flow of
unlbaleled molecules which goes in the cell too. It is been followed by unlabeled molecules. There is a flux of runnnig
fliuisd, while cell is intact. The pigmneted epithelium cell is eating the top of the photorecptor cell. It’s a phagocytic
cells, Its biting off the membrane, indgesting and degrading them. there is constant synthesis of material by the
biosntheric pathway. Or the cell would grow right?
Example of tunroveR in our bodies:
Bones are continually turned over.
This is an extracellular example. We
continually have cells called osteoclasts
which are eating and emlininating our bones.
You have cells called osteoblasts. They eat
our bones and eliminate them.
The image is a extracellular matric molecules,
packed version. Ver dense.no cells, just
There are the osteoclasts moving away, whie
eatng. secreted acids and digestive acids had
broken down and destroys the bone. We
have another type called the osteobalsts
which continue to secrete the bone.
The balance between the two is critical for
the bone structure.
Osteoprosis is the imbalance between
osteoclasts and osteoblasts. Too much bone
destruction and not enough reuilding of
BIO230 Page 5 Now lets look at cellular turnover.
This can be stem cell dependent or stem cell
When we decide if its stem cell dependent or
independent we need to know the definitoin
of stem cel.
Stem cell : is not differnetiated.
In previous elctures we saw the begninning
cells where genes were asked to turn on or
off. Stem cells don’t do that. They are not
They can divide unlimitedly. Their dayghters
can remain a stem cell or they can
Stem cells don’t tell to turn on / off genes. It
stays in the same exact state it was. The
Terminally differentiatied daughters either remain as stem cells or they
Without limit differentiate.
This differentiation is the same kind of choice
we taling eabout in the fdevelopment of
This is breaking the rule of stem cell: because
it happen from stem cell differntaition. This
can occur in the liver. If you cut the liver in
half it will grow until it regrow the size where
the cells need to.
Oancreas; diffentiated cells renewig the
There should e specific mechanisms for the
stem cells to work in the life time of the
BIO230 Page 6 The fate of stem cell daughters have to be
This can be controlled in two ways, to both
maintain the stem cell population and to
control how the other daughters diffentiate.
You can see from the examples that the
concepts are identical to what we saw in th e
differentiation lecture in embryogenesis.
One case is divisional asymetry.:
Intrisic mechanims prmotng cell
Can’t be restored differntiatinn.
Red factors promite asymetric cell
differntiation. The one that doesn’t recive
that factor differentiate.
If the stem cells are lost the original members
cannot be regenerated.one stem cell makes
one stem cell. If you have 100 stem cells, you
get 100s stem cell. If you break this by 50
then you get 50 stem cells. That’s the
concern about the mechanism, you can lose
the population and its difficult to restore.
Identical to the extrinsic cue. Daughters are
born the same, but born into different
environments. Cell divison is symettric and
Fate is determined about the environment.
The nice thing about the mechanism is if
stem cells are lost, their numbers can be
increased by both daughters entering division
by promting stemness.
If you have two many stem cells let both
daghtersgo into the envirnoement to
So there is regulation possible in this system
BIO230 Page 7 If the stem cells were to last an entire life
time of the organisms, you can imagine if we
were born with a certain number of stem
cells,how does it last an entire lifetime? Cell
divisions have problems with them. there
are mutations associated with the division of
cells. Packing and moving of the dna leads to
muations. Every time a cell divides it gains
mutations. Everytmie the cell divides
telomeres gets depleted.
If the cell divides too much it gains
mutations. Its chromsomes are getting
unstable because of the loss of telomeres. So
cells overcome this by dividing slowly. So it
divides only a couple of times during the life
It divides much more slowly.
So then how do we make enough cells to
make a tissue of the stem cells divide slowly?
There is a cell type stage which is called
the transit amplifying cell. This occurs just
as soon as the stem cell has divided. We
can see the stem cells has renewed itself.
And the other daughter has gone to
Before it diffenrtiatie ts it starts to divide
like crazy. This is where it catches up it can
divide rapidly. It doenst matter if it divides
lot. Because it is differntiaite. Okay for I
tot gains mutaions because it is already
diffenttiated and will bne perfomrin tht
enoirmal functions of the tissue.
This ica resuppy the tissue and maintain
the tissue structure.
BIO230 Page 8 Third concept: stem cell Niche: specific
environment that helps promote the stem
It will supply the signals which will
promote stemness and maintain the stem
A nice example is the skin stem cells
which reside in the basal layer and require
attachment to the basal lamina to remain
a stem cell. Balsal lamina provides the
niche. Picture: The base of the skin:
This epithelium layer is unique and its
stratified. That means have multiple cell
layers in the epithelium. The base is in
contact with the ECM like any other
epithelium. The basal lamina is just a sheet
of extracellular material.not cellular
material but its extracellular fibre