Stem Cell Bio Exam 2 Study Guide
Stem Cell Bio Exam 2 Study Guide 3260
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This 9 page Study Guide was uploaded by AnnaCiara on Friday April 1, 2016. The Study Guide belongs to 3260 at University of Connecticut taught by Dr. Conover in Spring 2016. Since its upload, it has received 66 views. For similar materials see Stem Cell Biology in Physiology at University of Connecticut.
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Date Created: 04/01/16
PNB 3260 Stem Cell Bio Exam 2 Study Guide 1. Describe the adult stem cell niche. 2. What is a transit-amplifying (TA) cell? Where did it come from and what does it become? 3. What is symmetric division? 4. What is asymmetric division? 5. List 6 examples of locations of stem cell niches. 6. What is the importance of adherens junctions in the stem cell niche? 7. What is the role of villi in the intestine? 8. Where are intestinal stem cells (ISCs)? What are they responsible for? 9. What type of cells line the crypt? 10.List 5 examples of differentiated progenitor cells. 11.Describe the inner lining of the stomach. 12.How is pepsin generated? 13.Describe pylorus organization. 14.What stimuli can change fate-restricted niches? 15.Define niche. 16.What are the cell types in the central nervous system (CNS)? 17.Describe neurogenesis of the ventricular system in the embryo. 18.What are the two different regions of neurogenesis in rats? 19.What are the 4 cell types in the subventricular zone (SVZ) niche? 20.How are neural stem cells detected? 21.List the types of astrocytes in the SVZ. 22.What is the function of the SVZ? 23.When does neurogenesis in the SVZ stop in a human? 24.What is a main benefit of neurogenesis? 25.What factors influence neurogenesis? 26.What factors promote neurogenesis? What causes an increase of these factors? 27.Besides neurons, what are the longest cells in the body? 28.What is a satellite cell? 29.What is Fibrodysplasia Ossificans Progressiva (FOP)? What causes it? 30.What is a fate map? 31.What happened to myoblasts exposed to BMP stimulation? 32.What is the role of Tie2+ progenitors? 33.What is the main function of the stomach? 34.Describe the cell types and secretions in the stomach. 35.Describe the migration and differentiation of stem cells in the stomach. 36.What is the function of the small intestine? 37.What is the differentiative ability of an intestinal stem cell (ISC)? 38.What is the function of the large intestine? 39.How are crypts in the large intestine “self-organizing”? 40.What happens when BMP is knocked out? 41.What happens when Noggin is overexpressed? 42.What is Wnt signaling? What happens if it is disrupted? Hyper-activated? 43.What happens when a cell leaves an area that has Wnt? 44.Discuss the relation between gastrointestinal cancer and colorectal cancer. 45.What happens when Wnt stimulus is present? 46.What happens when Wnt stimulus is absent? 47.Describe the signaling pathways and their respective resulting cell lineages. 48.What are Lgr5+ cells? Where are they located? 49.What happens when the stem cell niche in the crypt of the large intestine is injured? 50.What are the functions of skin? 51.List the similarities and differences between human and mouse interfollicular epidermis. 52.What are the 3 main regenerative processes in the skin? 53.Describe the cycle of growth in the hair follicle. 54.Describe the proliferation that occurs in the hair follicle. 55.TRUE or FALSE: Adipose precursors proliferate BEFORE activation of the hair follicle. 56.TRUE or FALSE: Hair growth (induction of anagen) REQUIRES immature adipocytes. 57.Describe the role of adipocytes in the hair follicle. 58.Describe the role of BMP in the hair follicle. 59.What are the 3 phases of the wound healing process? 60.How is healing affected if the injury involved a depletion of adipocytes? 61.TRUE or FALSE: fibroblast repopulation REQUIRES new immature adipocytes. 62.What is a hematopoietic stem cell (HSC)? 63.What lineages arise from HSCs? 64.List 3 sites of sites of blood cell formation. 65.What causes a major change in the main location of hematopoiesis? 66.What is FACS? 67.What is parabiosis? 68.What are the two different types of parabiosis? 69.What are the effects of sleep deprivation on HSC transplantation in mice? 70.What is one reason for the negative affects of sleep deprivation? Answer Key: 1. The adult stem cell niche is: a. Unique to each organ or tissue type b. Quiescent within its niche, infrequently divide c. In microenvironment that limits proliferation and differentiation d. Necessary for daily injury repair/cell replacement 2. A transit-amplifying (TA) cell is an adult stem cell that rapidly divides but differentiates into a specific cell type after a limited number of divisions. a. Stem cell à TA cell à TA cell divides many times à each becomes progenitor cell à each progenitor becomes a differentiated cell 3. Symmetric division: 2 types a. Stem cell à 2 stem cells b. Stem cell à 2 TA cells **CELL LINE IS LOST** 4. Asymmetric division: Stem cell à 1 stem cell + 1 TA cell 5. Examples of locations of stem cell niches: a. Germanium of ovary b. Apex of testis: number of stem cells limited by amount of somatic cells present that can be attached to c. Subventricular zone (in brain) i. Additional niche in brain = epithelial cells that line ventricle generate stem cells that help circulate cerebral spinal fluid d. Bulge (in hair follicle) e. Crypt of intestinal villus f. Bone marrow: can make myloid or lymphoid lineages 6. Adherens junctions help keep stem cells in the niche. 7. Villi make up the lining of the intestine and largely increase its surface area. Additionally, every villi has a crypt and every crypt helps add cells to the villa lining 8. Intestinal stem cells (ISCs) are found in the crypt of the villi in the intestine: below the progenitor cells and above the paneth cells. There are 2 locations where they are found in the crypt: the +4 position and the stem cell zone (CBC stem cells here – may be more proliferative). ISCs are responsible for regenerating the entire cell population of the villus ever 3-5 days. Cells contantly shed from top of villus and are replaced by differentiating and migrating cells created in the crypt from mitotic renewal. 9. Pericryptal fibroblasts line the villi on the mesenchymal side. 10.Differentiated progenitor cells: a. Absorptive enterocytes b. Goblet cell c. Paneth cell d. Entero-endocrine cell e. Tuft cell 11.The inner lining of the stomach is lined with epithelium. Gastric glands in the lining are lined with mucus cells, chief cells and pariental cells. 12.Pepsin synthesis: a. 1) Chief cells secrete pepsinogen b. 2) Parietal cells secrete hydrochloric acid (HCl) c. 3) Pepsinogen interacts with HCl to make pepsin d. 4) Pepsin further interacts with HCl and pepsinogen to make more pepsin 13.Pylorus a. Most inner: gland (from bottom contains base, neck, and isthmus) i. Lgr5 +ve stem cells here – removed stem cells and made organoid similar to stomach b. Upper: pit 14.Stimuli that can override fate-restricted niches: wounds or mechanical stress. 15.Niche: the dynamic microenvironment that surrounds and influences stem cells, allowing a diversity of cell types. Researchers often struggle to create niches like the ones found in vivo because of the dynamic nature of natural niches. Microfluidics may help solve the problem. 16.CNS cell types: a. Neurons b. Glia i. Oligodendrocytes ii. Astrocytes iii. Ependymal cells iv. Microglia 17.Neurogenesis of the ventricular system: BVs = Brain Vesicles; WM = White Matter Primary BVs Secondary BVs Adult Brain Structures Cerebrum: cerebral Telencephalon hemispheres (cortex, WM, basal nuclei) Prosencephalon 1- Diencephalon: (forebrain) thalamus, Diencephalon hypothalamus, epithalamus 2-Retina Mesencephalon (midbrain) Mesencephalon Brain stem: midbrain Metencephalon Brain stem: pons Rhombencephalon Cerebellum (hindbrain) Brain stem: medulla Myelencephalon oblongata N/A N/A Spinal cord 18.Two different regions of neurogenesis in rats: a. lateral wall of the lateral ventricle b. the hippocampal dentate gyrus. 19.4 cell types in the subventricular zone (SVZ) niche: a. 1) Ependyma: multiciliated, motile, post-mitotic b. 2) Type A (neuroblasts): highly migratory immature cells c. 3) Type C (TA progenitors): highly proliferative, immature phenotype d. 4) Type B (astrocytes): slowly dividing cells that surround neuroblasts 20.1) Neural stem cells are detected by incorporating [H ]-thymidine into the DNA during the S-phase of replication. 2)BrdU (bromodeoxyuridine), a synthetic thymidine analog can be incorporated in S-phase then detected with immunochemistry. 3) Retroviral vector put into genome of proliferating cells and passed to progeny 21.Types of astrocytes in the SVZ a. Structural/niche cells b. Stem cells – similar to radial glia i. Help with ependymal repair ii. Helps with repair of SVZ after damage (injury/disease) 22.The SVZ makes the olfactory bulb’s GABAergic interneurons that are important in fine odor discrimination. These interneurons make up the granule and periglomerular regions. 23.Neurogenesis in the SVZ stops when a human is 2 years old. 24.Main benefit of neurogenesis is that new information is stored with newly made neurons while old information is unharmed. 25.Factors influencing neurogenesis: a. Increased by: i. Learning ii. Exercise iii. Antidepressants b. Decreased by: i. Stress ii. Aging 26.Factors that promote neurogenesis (increased by pathological conditions - seizures) a. BDNF b. VEGF c. IGF d. FGF2 e. Neuropeptide Y 27.Outside of the CNS, the longest cells in the body are in skeletal muscle tissue. Skeletal muscle cells are called muscle fibers (they are long and multinucleated). 28.A satellite cell is a muscle stem cell. This is the cell responsible for muscle’s regenerative ability. They are ONLY found in skeletal muscle but may be able to differentiate into more cell types (fat, connective tissue, bone). 29.FOP is an autosomal-dominant disease with inappropriate bone growth in the skeletal muscle or soft tissues, starting in childhood or early teens. It is caused by a mutation (R206H) in the BMP Type I receptor (ACVR1). 30.A fate map shows development stages of an organism and indicates the fate of cells and regions. This is important for successful grafting, isolation and experimental treatments for FOP. 31.Myoblasts exposed to BMP stimulation increased osteogenic markers (ALP, Runx2, Osterocalcin) and decreased myogenic markers (MyoD, Myogenin) à giving an osteogenic phenotype. 32.Tie2+ progenitors mediate heterotopic ossification (injury-induced and spontaneous). 33.The main function of the stomach is to digest proteins. The acidity of the stomach activates proteases. 34.Stomach cell types and secretions Cell Type Secretion Mucous neck cell Mucus and bicarbonate Gastric acid (HCl) and intrinsic factor Parietal cell (for Ca2+ absorption) Enterochromaffin-like cell Histamine (important for acid stimulation) Chief cells Pepsin(ogen) and gastric lipase D cells Somatostatin (acid inhibition) G cells Gastrin (acid stimulation) 35. Migration/differentiation of stem cells in the stomach: cells starts as Lgr5 +ve stem cell in gland bottom then migrates upwards towards the pit and differentiates into a TA/progenitor cell then migrates to the pit and differentiates into a mucin 6 producing cell that continues to migrate up to the top of the pit until it dies and is sloughed off (*EXCEPTION* paneth cells migrate DOWNWARD – towards the bottom of the gland). 36.The small intestine functions to digest carbohydrates and lipids AND absorb nutrients. 37.An intestinal stem cell (ISC) –located in bottom of gland - can differentiate into: a. Absorptive cell: located at mouth of crypt and line the villi b. Secretory cells: i. goblet cell: located sporadically between absorptive cells ii. enteroendocrine cell: located sporadically between absorptive cells iii. paneth cell: located in base of crypt next to stem cells (stem cells attach), live up to 6 weeks 38.The function of the large intestine: a. Continue vitamin absorption b. Water absorption 39.The self-organization of crypts in the large intestine: a. Formation of crypt à i. Stimulated by sonic hedgehog signaling in mesenchymal cell of underlying tissue (hedgehog signals concentrated in intervillus space) 1. HH signaling activates BMP secretion 2. à BMP-2 and BMP-4 secreted from mesenchyme to form villi ii. Inhibited by BMP signaling iii. Noggin (BMP inhibitor) secreted in crypt b. Formation of villi à i. HH signaling activates BMP secretion ii. à BMP-2 and BMP-4 secreted from mesenchyme to form villi iii. BMP promotes differentiation of cells in the villi 40.BMPR1A knock out à EXCESSIVE CRYPT DEVELOPMENT a. Clinical disorder in humans: Juvenile Polyposis Syndrome – a mutation in BMPR1A or SMAD4 a downstream effector of BMPs 41.Noggin overexpression à EXCESSIVE CRYPT DEVELOPMENT a. BMP factor that blocks crypt formation via HH b. Noggin protects epithelium from BMP action 42.Wnt signaling a. Wnt & receptors are in both in crypt b. Signaling promotes/maintains proliferation – keeps cells in crypt dividing c. Stops differentiation (EXCEPT paneth cells) d. Pathway disrupted à loss of crypts and reduction in number of villi e. Hyper-activation à huge crypts are formed f. Maintenance of stem cells done by releasing Wnt in response to Wnt 43.When a cell leaves an area that has Wnt, the cell can take on potential to become a differentiated cell. As a cell loses Wnt signaling it starts to express EphrinB1. Ephrin2/3 expressed in stem cell niche. 44.Colorectal cancer: a. A type of gastrointestinal cancer b. One of leading causes of cancer-related deaths c. Most are caused by mutations in important parts of the Wnt pathways (APC – tumor repressor gene mutated) d. Gastric cancer is close in frequency/deadliness 45.Wnt stimulus is present: a. Wnt binds to Frizzled-Lrp5/6 (receptor) and LRP (accessory receptor) b. Inhibits APC c. Beta-catenin is stabilized, accumulates and goes to nucleus d. Stimulates Tcf transcription factors (beta-catenin binds to Tcf) e. Activates transcription of Wnt/Tcf target genes 46.Wnt stimulus is absent: a. Proteosomal degradation: APC destruction complex causes beta-catenin to have shortened half-life 47.Signaling pathways and resulting cell lineages a. Wnt signaling à secretory cell lineages b. Notch signaling à absorptive cell lineages (also inhibits secretory cell lineages-enterocyte lineage) 48.Lgr5+ cells a. Lgr5 is a G-protein coupled receptor; is a downstream target of Wnt signaling b. Located at base of crypt c. Rapid division 49.Injury to crypt (ex: radiation) a. à Lgr5+ve CBC stem cells die but paneth cell niche survives b. à Regeneration: i. 1) epithelium regenerated from Lgr5+ve cells that survived ii. 2) TA cell plasticity - go back into niche and regain stem cell identity 50.Functions of skin: a. Protection: from pathogens and environmental damages b. Prevent water loss c. Thermoregulation d. Absorption (gas exchanges) e. Sensory input f. Social cues 51.Similarities and differences between human and mouse interfollicular epidermis: a. Similarities i. Epidermal layering: stratum corneum (dead), granular layer, spinous layer, basal layer, basal lamina b. Differences i. Mouse: single layer of granular layer and spinous layer ii. Human: multi-layer granular layer and spinous layer iii. Basal layer in human is wave shaped not straight (mouse) 52.3 main regenerative processes: a. InterFollicular Epidermis (IFE) i. New upper layers every 4 weeks ii. Proliferate of cells and differentiation in basal layer the move outward iii. Outer most layers shed b. Hair Follicle (HF) i. 2 regions: epithelial and mesenchymal c. Wound Healing 53.Hair follicle cycle of growth: a. Anagen (growth) à catagen (regression) à telogen (rest) à early anagen 54.Proliferation in the hair follicle: a. Catagen à telgogen: Bulge cells migrate to hair germ b. Telogen-anagen: Hair germ proliferates c. Anagen: Bulge cells self-renew 55.TRUE: Adipose precursors proliferate BEFORE activation of the hair follicle. 56.TRUE: Hair growth (induction of anagen) REQUIRES immature adipocytes. Additionally, immature adipocytes are a sufficient stimulus for hair growth via the dermal papilla. 57.Hair follicle growth à cytokine secretions from epithelial section à cytokines activate adipogenesis à BMPs derived from adipocytes inhibit hair growth AND mature adipocytes inhibit activation of stem cells in the hair follicle a. Niche is created by adipocyte lineage to regulate stem cells in the hair follicle 58.BMP (believed to be mature adipocyte derived) keep follicles in rest state and prevent them from growing. 59.3 phases of wound healing process a. 1- inflammation phase day 1-3 i. mature adipocytes contribute b. 2- proliferation phase 3-7 i. more cells than existed in uninjured cells ii. proliferating adipocyte precursors (preadipocytes) are present iii. need to prune away extra cells c. 3- remodeling phase 7-21 i. scar - injury too big ii. inducible dipseria toxin receptor 60.If injury involves a depletion of adipocytes, then revasularization and re- epithelialization are less effective. 61.TRUE: fibroblast repopulation REQUIRES new immature adipocytes. 62.Hematopoietic stem cell (HSC): stem cell that matures into blood cell via hematopoiesis and 63.HSCs can generate 2 lineages: a. Myeloid à neutrophils, basophils, eosinophils, erythrocytes, platelets b. Lymphoid à T cells and B cells 64.Sites of blood cell formation i. Yolk sac (extra-embryonic) ii. Fetal liver iii. Bone marrow (most common site for adults) 65.The severing of the umbilical cord changes the site of hematopoiesis to mainly be the bone marrow because there is a major change in blood flow that results in the loss of nestin pericytes and alteration of the HSC niche in the fetal liver. 66.FACS stands for Fluorescent Activated Cell Sorting – a method which uses a laser on each single cell to isolate certain cell types based on charge. Steps: a. 1) fluorescently label undifferentiated stem cells (fluorescent tag attaches to the surface marker of the cell receptor) b. 2) cell pass through one by one and are shown on by a laser c. 3) fluorescently marked cells will have a negative charge and non marked cells will have a positive charge 67.Parabiosis: surgically joining two organisms (mice in this case) so they share circulation. 68.Two kinds of parabiosis a. isochronic: 2 aged mice (aged-aged) b. heterochronic: one aged one young (aged-young) 69. Sleep deprivation of the donor during a HSC transplantation results in a 50% reduction in ability of the transplanted cells to properly engraft and reconstitute blood and bone marrow AND thwarts migration/homing of HSCs. 70.Growth hormone is secreted during sleep, which may be one reason for the negative affects of sleep deprivation.
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