Crypt Stem Cells Article Background
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What is tissue specific?
it is a kind of cell specific because tissues have a lot of cells
Embryonic stem cell?
- has the fate to become anything
- --> the further along in differentiation you become, the more restricted they come
Colon cancer derives from __
epithelial cells, which go bad--> not other stuff
Villi in the intestine do what?
increase the surface area, which eventually increase the absorption
How long do cells usually live in the intestine?
- five days
- cells are damaged by environment and accumulate DNA damage
What are the dynamics involved with renewal?
There are stem cells in the crypts, which divide slowly. Daughter cells rapidly divide and replace cells along the villus
Explain stem cells in all of our tissues
WE have stem cells in all of our tissues, maintained by adult stem cells. It is not that they can become anything, but things in their lineage
hormonal and respond to signals
hang out by the stem cells and maintain the environment that allows stem cells to survive
involved in absorption
What is the division of stem cells?
asymmetric: one daughter cell differentiates and hte other remains a stem cell
After division, what does the ES become?
it becomes a transit amplifying cell, which replicates several more times before differentiating more and moving up
Wnt signaling pathwa
- directs cell proliferation
- when cells emerge from the crypt, that's when they differentiate and do their job, eventually undergoing apoptosis
Every 3-4 days, you have to replace your cells
What can happen to TACs?
- they can fail to stop dividing
- failure of cells to stop dividing
- or terminally differentiated cells can revert back to TACs
In the crypts are?
dozens of stem cells, which proliferate and become TACs and aeventually differentiate to become other cells
--> it is like a conveyor belt
What is differentiation?
a cell makes a commitment to an ultimate lineage or fate
How do you silence genes that will not be used?
turn them into heterochromatin
What happens as you commit to a pathway?
you end up with a genome that has heterochromatin turning/ closing off vast portions of your genome and leaving only the stuff that can be transcribed and allow for the differentiation
What does commitment rely on in liver cells?
the Wnt Pathway
Active wnt pathway?
proliferation is on and differentiation is put off
Inactive Wnt pathway?
as cells emerge from the villus, they stop proliferating and begin differentiating
Without Wnt signaling, what happens?
complex of proteins, one being APC, binds beta-catenin in an APC complex. It is phosphorylated by GSK, leading to degadation of beta catenin
- has other fates
- also part of a complex of proteins in cell-cell junctions; any additional Beta-catenins bound by APC are degraded
With Wnt signaling, what happens?
A ligand, which binds a receptor--> active/ protein in APC complex is phosphorylated--> no longer able to bind Beta-catenin--> no degradation
If beta-catenin is not degraded, what can happen?
- it translocates into the nucleus where it finds transcription factors.
- TCF/LEF together turn on transcription for genes involved in proliferation (cell transits from G1 to S phase)
Essentially, Beta catenin not being degraded allows what?
allows accumulation and binding to TCF/LEF, which bind and allow expression of proliferative genes
Explain outside of the crypts.
outside of the crypts, there's no Wnt present (soluble factor). APC binds to Beta catenin, which is phosphorylated by GSK, and degraded
The Wnt pathway regulates Beta catenin via __, without which Wnt can't regulate Beta-catenin.
For sporadic colon cancer, what is the probable cause?
loss of APC, causing Beta-catenin to not be degraded
bone morphogenic peptide
inhibits production of Wnt, leading to APC not eing phosphorylated and thus not allowing beta catenin to bind
A lot of Wnt present leads to __
There are inherited versions of colon cancer.
- FAP--> One defective copy of APC
- To get colon cancer indefinitely, both APC genes need to be knocked off
polyps appear everyowhere
is related to the processes of tissue renewal
Enterocytes live for __
Explain epithelial cell migration.
From birth at the bottom of the crypt to the loss at the top of the villus; transit time is 3-6 days
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