Final Flashcards
_______ is necessary to maintain tissue function
Cell Renewal
What cell types are capable of re-entering the cell cycle and replacing damaged/lost cells?
fibroblasts and endothelial cells
Describe why cell renewal is necessary to maintain tissue function
Most somatic cells are arrested in G0 and do not proliferate
Cells in tissues may be lost due to DNA damage, injury, apoptosis etc.
New cells must replace these damaged/dead cells in the tissue – cell renewal
What is endothelial cell proliferation is driven by?
The growth factor VEGF
What can damage to endothelial cells/blood vessels lead to?
Hypoxia – tissue is not receiving enough oxygen
What does tissue hypoxia promote?
vascular endothelial growth factor production (VEGF) secretion, which in turn promotes endothelial cell proliferation through RTK signaling
What do endothelial cell do in response to VEGF?
Endothelial cells proliferate and form new capillaries (angiogenesis), which innervates the hypoxic tissue with new blood vessels
Describe the four stages of Wound healing
- Hemostasis
- Inflammation
- Proliferation
- Remodeling
Describe the four stages of wound healing
Hemostasis – cessation of blood flow: blood vessels constrict to minimize blood flow/loss, platelets promote clot formation, fibrin (fibrous protein) cross links platelets in clot
Inflammation – immune cells travel from bloodstream to wound site, fluid build up and immune cell extravasation promoted by vasodilation of blood vessels (swelling), increasing blood flow (redness)
Proliferation – fibroblasts enter wound site and secrete ECM components including collagen, rebuilding lost ECM. Epithelial cells continue to proliferate and close wound, myofibroblasts help pull damaged tissue together, new blood vessels form to innervate newly formed tissue through angiogenesis
Remodeling – collagen fibers are remodeled (type III to type I), new epithelium is fully formed and scar tissue forms
What do fibroblasts differentiate into?
A specific subtype of fibroblast called the myofibroblast
When do myofibroblasts form?
Myofibroblasts form from differentiation of fibroblasts during wound healing
What do myofibroblasts do?
Myofibroblasts are contractile cells that promote wound healing by pulling damaged tissue together using smooth muscle type actin and myosin during the proliferation phase
This differentiation process is driven by mechanical tension and the cytokine transforming growth factor-β1 (TGF-β1)
What is the average lifespan of the human liver cells?
200-300 days
Describe two aspects of liver regeneration
- Liver cells are arrested in G0 but capable of re-entering cell cycle
- Liver regeneration is done by normal differentiated liver cells in response to specific extracellular signals
Describe a fact about rat liver removal
In rats, surgical removal of 2/3 of the liver leads to full regeneration of liver in a few days
What are most cells in adult tissues are replaced by?
The proliferation and differentiation of stem cells
Define stem cells
Stem cells - undifferentiated cells with the potential for self renewal and differentiation
What are stem cells capable of?
Stem cells are capable of asymmetric cell division, producing one stem cell and one differentiating cell through mitosis (can also produce two stem cells through mitosis)
What are trasit-amplifying cells?
undifferentiated cells in transition from stem to differentiated cell
Define differentiation
process of becoming a specialized cell type – involves large changes in gene expression (epigenetics, chromatin remodeling), also changes in cell morphology, metabolism etc.
What is a hematopoietic stem cell (HSC)?
a classic model of a self-renewing stem cell that gives rise to a multitude of differentiated cell types
Describe the different types of blood cells
Erythrocytes – red blood cells, transport oxygen and CO2
Platelets – fragments of megakaryocytes that promote clot formation
Macrophages – phagocytic cells involved in both innate and adaptive immunity
Granulocytes – white blood cells with immune functions, characterized by secretory granules
B and T lymphocytes (B cells and T cells)– white blood cells involved in adaptive immune response
How many blood cells does the human body produce in a day?
100 billion
What does the maintenance of blood cell populations depend on?
Adult blood cells do not proliferate – maintenance of cell populations depends on hematopoietic stem cell population maintenance
What do all of the different types of blood cells develop from?
hematopoietic stem cells in the bone marrow
What makes bone marrow transplants possible?
The vast potential of HSCs
What are some of the most proliferative stem cells in the body?
Intestinal crypt stem cells
What is the lifespan of the intestinal epithelium?
A few days, exposed to harsh environment, billions of cells shed each day
What replaces lost epithelial cells in the intestines?
Stem cells at the base of intestinal crypts continually divide and replace lost epithelial cells
What makes up 2/3 of the intestinal crypts?
Transit amplifying cells
What is a niche?
An extracellular environment that maintains stem cells
Stem cells reside within specific microenvironments called _______
niches
What do niches provide?
provides environmental signals that maintain stem cells/balance their self renewal and differentiation
In the intestinal crypt, what helps maintain intestinal crypt stem cells?
Paneth cells and Wnt-producing fibroblasts secrete Wnt polypeptides that help maintain intestinal crypt stem cells
Describe the several stem cell compartments of mammalian skin
Epidermal stem cells differentiate into transit-amplifying cells, which differentiate into new epidermis cells
Bulge stem cells give rise to transit-amplifiying matrix cells, which differentiate and form the hair shaft
Sebaceous gland stem cells maintain the sebaceous gland, which secretes oils to protect the skin
What is the muscle stem cell?
The satellite cell
Describe stem cells in the skeletal muscle
Satellite cells – stem cells in muscles located beneath basal lamina of muscle fibers
The progeny cells of satellite cells differentiate and fuse into new muscle fibers
True or False: Skeletal muscle is capable of rapid regeneration in response to damage (injury, exercise)
True
Embrionic stem cells are _______
totipotent: able to give rise to all tissues
Give the hierarchy of stem cell differentiation ability
Totipotent > Pluripotent > Multipotent
what kind of state are embryonic stem cells grown in?
An undifferentiated state.
Embryonic stem cells can be induced to form ______ and then differentiate into a variety of cell types.
embryoid bodies
Describe Somatic cell nuclear transfer and cloning
- Nuclei from adult somatic cells are transferred to enucleated oocyte
- 1-2% of embryos generated give rise to adult with identical genetics (clone)
- Epigenetic reprogramming necessary to give
rise to all cells in clone
- Limited lifespan
Describe Therapeutic cloning
- Similar process (adult somatic cell nuclear transfer)
could be utilized for therapeutic cloning - Generation of clonal embryonic stem cells
- Stem cells could then be differentiated in vitro to
give rise to cells and tissues for transplant
- Identical genetics – no risk of
transplantation rejection
What TF are able to reprogram somatic cells to a pluripotent state?
A cocktail of transcription factors termed the Yamanaka factors
Describe how we are able to reprogram somatic cells to a pluripotent state
- A cocktail of transcription factors, termed the Yamanaka factors, are able to reprogram somatic cells to a pluripotent state.
- This allows adult fibroblast cells to be “reprogrammed” into induced pluripotent stem cells through the expression of specific transcription factors.
- Takashi and Yamanaka introduced Oct4, Sox2, Klf4, and c-Myc transcription factors through a retroviral vector which infects the somatic cell.
- An induced pluripotent stem cell is then produced, which functions similar to embryonic stem cells – capable of differentiating into all cell types.
How do Yamanaka factors work?
They act synergistically to repress differentiation genes and open chromatin and activate transcription of pluripotency genes.
- Yamanaka factors form a positive feedback autoregulatory loop that maintains pluripotency in both induced and embryonic stem cells
- The function of these transcription factors activates transcription of pluripotency-promoting genes and represses expression of differentiation genes
What is c-Myc?
A proto-oncogene that promotes proliferation of stem cells – can lead to risk of tumor development following stem cell implantation
What was found to be dispensable in the production of induced pluripotent stem cells?
Nanog
What is Transdifferentiation?
The direct conversion of cells from one fate to another.
The direct differentiation of a differentiated adult cell into another differentiated lineage
True or false: Differentiated blood cells can also transdifferentiate to other blood cell types, but NOT hematopoietic stem cells
False: they CAN transdifferentiate into HSCs
(ex: leukocyte can go to granulocyte; leukocyte CAN ALSO go to hematopoietic stem cell)
How can transdifferentiation occur?
Through mutations accumulated in cancer cells i.e. leukemia, lymphomas.
What is the extracellular matrix (ECM)
A network of proteins, polysaccharides, and other components that fills the spaces between cells and binds cells and tissues together
Where is ECM most abundant?
In connective tissues – tendons, bones, cartilage
What is the basal lamina?
A thin sheet of ECM that supports epithelial cells, also surrounds muscles and peripheral nerves
What is ground substance?
Fibrous proteins embedded in a gel-like matrix of polysaccharides that makes up the ECM
What are fibroblasts?
Specialized cells that secrete ECM
What are chondrocytes?
Chondrocytes secrete collagen and other extracellular matrix components to form and maintain cartilage
What is the most abundant ECM protein?
collagen
What kind of structure does collagen form?
Individual collagen polypeptides wind together forming a triple helical structure resembling a rope
What does the triple helix domain of collagen contain?
It contains regular G(glycine)-X(often proline)-Y(often hydroxyproline) repeats to allow for tight packing (glycine required in every 3rd position)
What is Hydroxyproline
A modified proline residue formed in the ER lumen
True or false: Collagen helices are stratified and cross linked into fibrils
True
What do Fibrils help contain?
The gaps between collagen triple helices that contribute to flexibility
Do fibrils form inside the cell?
No, Fibrils do not form within cells – procollagen is cleaved to collagen following secretion from the cell
What has has regular breaks in its helical domain?
Type IV Collagen
Describe Type IV collagen
Type IV collagen forms networks rather than fibers – key role in formation of basal lamina
G-X-Y domain in helical region is interrupted by nonhelical domains – cannot form fibers
Type IV collagen is more flexible than fiber-forming collagens
What is the makeup of a Glycosaminoglycan (GAGs) ?
repeated disaccharide chains which often contain sulfate groups