epithelia II B Flashcards
Epithelia undergo continuous development though:
Epithelial stem cells, cell division, and differentiation
epithelia generally contain stem cells that are capable of cell division, and that serve to
- self renew: regeneration of stem cells with each division
2. produce differentiated cell types specific to each epithelia.
Like all stem cells, epithelial stem cells:
replace cells that die and can flexibly regulate (change) the form and function of tissues
Stem cells produce
differentiated cell types by cell division coupled with specific pathways of cell specification imposed on some of their daughter cells.
Many stem cells produce
daughters that also proliferate themselves (undergo cell division cycles), often at faster rates; these transitional intermediates are called transit amplifying cells.
transit amplifying cells produce:
differentiated cells, either directly or through several steps of specification
At each step, specific changes in protein expression patterns and activities occur.
______ determines the constellation of cell types, their relative proportions, and their arrangements.
The developmental state of stem cells
A specific stem cell type, its intermediate progeny, and their differentiated progeny are collectively called a _____
cell lineage
Both division and differentiation in stem cell lineages are tightly regulated by ______.
cell to cell communication and cell signaling pathways, which are activated or inhibited by physiological and developmental cues
Because of tight regulation, stem cells typically divide _____
very slowly, or infrequently in some tissues.
they are usually much less abundant than their differentiated offspring.
Loss of tight regulation of stem cells is at the
heart of the many diseases of stem cell systems.
A typical cell signaling pathway consists of:
- an extracellular ligand (signal) secreted by signaling cells,
- a receptor in receiving cells that binds and is activated/inactivated by the ligand,
- downstream effector proteins in the cytoplasm and nucleus,
- numerous modulator proteins that promote or suppress pathway components.
Cell signaling of epithelial stem cells may be local involving _____.
ligands secreted by cells within the same epithelia or by cells in neighboring connective tissue
epithelial turn-over may be controlled by:
long-distance signaling between tissues.
Long distance signals are typically secreted from
endocrine glands into the blood stream (described below), or may be produced by the nervous system or other tissues.
Some of the most important signaling systems that control epithelial stem cell renewal and differentiation are:
- Wnt
- Sonic Hedgehog
- TGFβ
- Notch
- receptor tyrosine kinase family
(RTK; for example the EGF receptors) - FGF receptor
Each pathway is used by _____.
multiple, very distinct stem cell systems in different organs/tissues
Some pathway proteins may be ______
unique to certain stem cell subsets
most pathway components are ____
shared by several distinct stem cell lineages
stem cell lineages=
stem cells and all their daughters, granddaughters, etc
A single signaling pathway often triggers _____.
different developmental outcomes in different stem cell lineages
The pathway differences result from combinations of:
- Different developmental histories of each stem cell type (cells can inherit and maintain unique differences in nuclear (chromatin) and cytoplasmic states that are generated earlier in development, which dramatically impact how a cell responds to a ligand)
- Different environments stem cells reside in (or to put another way, the different combinations of signaling inputs a cell is exposed to).
- Differences in the levels of the extracellular ligands, receptors, and/or downstream components.
Defects in the______ lead to disease, particularly cancer. =
regulation, expression, or structure of signaling components (ligands, receptors, effectors)
Drugs that specifically target several components of these pathways are now in use as _____
one example:
anti-tumor agents
Tarceva (erlotinib) inactivates the EGF receptor and is commonly used to treat lung and pancreatic cancers