Harris Lecture 6 notes (1 per page)(1)-1

Harris Lecture 6 notes (1 per page)(1)-1 - All structures...

Info iconThis preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: All structures need maintenance Once cells and tissues are formed they continually regenerate This can occur at the level of molecular turnover or cellular turnover 1 1 Some tissues contain the same cells for the life of the organism, but the molecular components of these cells do turn over -typically cells with very specialized architecture e.g. auditory hair cells or photoreceptor cells Other tissues renew their cells rapidly -typically cells exposed to harsh environments or activities e.g. skin cells, gut cells or blood cells Other tissues are between these extremes 2 2 The specialized architecture of auditory hair cells in the organ of Corti no cells here 3 3 This architecture functions to convert sound waves in nerve impulses (it allows us to hear) Sound waves cause stereocilia atop hair cells to tilt With tilting, tethers pull open ion channels on neighbouring stereocilia (this initiate a nerve impulse) 4 4 This architecture functions to convert sound waves in nerve impulses (it allows us to hear) Sound waves cause stereocilia atop hair cells to tilt With tilting, tethers pull open ion channels on neighbouring stereocilia (this initiate a nerve impulse) 5 5 In mammals, these cells do not re-grow when lost Their loss from disease, toxins or extreme noise leads to permanent > hearing lost (Remarkably, other vertebrates can replace these cells) 6 6 Despite their stable overall structure, the hair cells and their stereocilia are very dynamicturningthe molecular level at over molecular component is filled with actin Actin cytoskeleton in a inner hair cell stereocilia bundle (adult mouse, width of picture 10 µm) www.uni-goettingen.de •The stereo cilia are filled and supported by actin •This actin undergoes continually polarized > treadmilling (assembly+ and disassembly•How can such dynamic machinery maintain the specific architecture 7 of the stereocilia for the lifetime of the animal? ) 7 Human photoreceptor cells are another permanent cell type with a specific architecture. Their architecture converts light waves into nerve impulses 8 8 The overall photoreceptor cells are permanent, but do they turn over at the molecular level? go into the epithelium Pulse-chase experiment -cells exposed to radiolabeled leucine for a short time -they take up the labeled amino acid and incorporate it into newly synthesized proteins for a short period of time Epithelial cells phagocytose (nibbling away) photoreceptors What will happen to the labeled Leucine? a) It will be detected in the cells for their entire lifetime b) It’s detection will gradually be lost 9 9 An extracellular example of molecular turnover: bone cell eating away the bone replaced by osteoblast The extracellular matrix that forms bone is continually digested by osteoclasts… …and deposited by osteoblasts Osteoblasts secret precursory bone material, which calcifies/solidifies. Some osteoblasts are 10 encapsulated into the bone. Too much osteoclast and too little osteoblast, weakening of the bone 10 Some tissues contain the same cells for the life of the organism, but the molecular components of these cells do turnover -typically cells with very specialized architecture e.g. auditory hair cells or photoreceptor cells Other tissues renew their cells rapidly -typically cells exposed to harsh environments or activities e.g. skin cells, gut cells or blood cells Other tissues are between these extremes 11 11 Cell turnover can be stem cell dependent or independent Stem cell definition 1. It is not > terminally differentiated 2. It can divide > without limit 3. Its daughters can 1remain a stem cell 2 or differentiate Cell renewal can occur from division of differentiated cells (e.g. liver cells and insulin-secreting cells of the pancreas) The use of stem cells requires specific mechanisms 12 12 The fates of stem cell daughters can be controlled in two ways 1. Divisional asymmetry One daughter receives factors promoting ‘stemness’, and the other receives factors promoting differentiation A drawback: If stem cells are lost, their original numbers > cannot be restored. Will drop. You get 1 from 1. stem cell differentiate 13 13 The fates of stem cell daughters can be controlled in two ways 2. Environmental asymmetry The cell division is symmetric and and the daughters’ fates are determined by the environment they are born in to If stem cells are lost, then their numbers can be increased by having both daughters of divisions enter the > environment promoting stemness 14 14 Stem cells divide slowly This protects the stem cell from: 1. Mutations associated with cell division 2. Telomere depletion associated with cell division stem cells minimize the effect by dividing slowly However, large numbers of cells are needed to renew differentiated cell populations 15 15 stem cells not affected Stem cells divide slowly fast division a few times Transit amplifying cells expand cell numbers before final differentiation 16 16 Skin stem cells and their progenitors The stem cells reside in the basal layer and require attachment to the basal lamina to remain as stem cells the basal lamina provides a niche for the stem cells stop the stem cells from differentiating After detaching from the basal lamina, the cells differentiate through a linear sequence of cell types and are finally shed from the animal some cells are pushed out of basal lamina and they will differentiate. 17 17 Skin stem cells and their progenitors The stem cells reside in the basal layer and require attachment to the basal lamina to remain as stem cells the basal lamina provides a niche for the stem cells After detaching from the basal lamina, the cells differentiate through a linear sequence of cell types and are finally shed from the animal Without renewal from stem cells, our skin would be lost in a month 18 18 Blood stem cells and their progenitors Blood stem cells differentiate into various progenitor populations creating a branched pathway to final differentiation Signals can promote specific branches depending on the need for cell types 19 19 Blood stem cells and their progenitors reside in bone marrow It will have no more blood cells produced. An electron micrograph of bone marrow Blood cell precursors are in bone marrow but are the stem cells there? If all blood stem cells were killed off would ‘new’ bone marrow restore them? This shows that the stem cells must be in the bone marrow. 20 20 Identifying blood stem cells and their progenitors Homogenize mouse bone marrow to release single cells Expose cells to fluorescent antibodies recognizing specific cell surface molecules Each antibody recognizes a cell surface receptor. Isolate labeled cells by Fluorescence-Activated Cell Sorting (FACS) separate the tagged cells from other cells with tag - charge no tag + charge Test ability of isolated cells to restore all blood cells of an irradiated mouse Cells with a specific set of markers can restore the blood cells => stem cells ~1/10 000 bone marrow cells can stem cells are rare ~5 of such cells are sufficient for the restoration 21 but powerful! 21 Blood stem cells are maintained through interactions with stromal cells in the bone marrow other cells in bone often are osteoblasts Once detached cells differentiate Stromal cells provides a niche for for the blood stem cells 22 22 Stem cells and their progeny must be regulated in many ways to supply the correct numbers of differentiated cells 23 23 Stem cells and tissue renewal affect how we age… …and can treat diseases and disabilities 24 24 Stem cells and tissue renewal affect how we age… …and can treat diseases and disabilities 25 25 Leukemia Patient's blood cells are cancerous 1. Patient undergoes radiation to remove all the blood cells 2. Inject donor's bone marrow Medical uses for stem cells Using blood stem cells to treat leukemia easy to isolate Problems of immune rejection careful tissue matching and immunosuppressive drugs if the cancer arises from a mutation in one of the progenitor populations then the patient's own stems cells can be used after sorting These stem cells are not cancerous! avoid immune response !! Or a patient Remove from marrow sample Inject the rest 26 26 Medical uses for stem cells What if the tissue to be replaced doesn’t have a readily available supply of its own stem cells? (e.g. spinal cord injuries or neurodegenerative diseases) Can cells of a different tissue be used to make stem cells for treatment? This occurs naturally during limb regeneration in newts •Muscle cells de-differentiate, become mono-nucleated and start dividing •A bud similar to the embryonic limb bud is formed from the cells •Their progeny form all of the cell types needed to re-grow the limb 27 27 Medical uses for stem cells What if the tissue to be replaced doesn’t have a readily available supply of its own stem cells? (e.g. spinal cord injuries or neurodegenerative diseases) Can cells of a different tissue be used to make stem cells for treatment? Current technology cannot do this from adult human cells at the scale or reliability needed for medical purposes, but is has been done in experiments This technique could avoid immune rejection by using the patient's own cells, but cancer development is a potential problem if cell differentiation isn’t properly controlled 28 28 Embryonic stem (ES) cells can proliferate indefinitely in culture and have full developmental potential This can increase the yield of cells needed for treatments, but ethical issues, immune rejection and the potential of cancer are still concerns 29 29 Two potential ways to avoid immune rejection of ES cells 1. Somatic cell nuclear transfer—use a nucleus from one of the patient’s own cells and transfer it into an unfertilized egg to develop an embryo from which ES cells can be harvested 30 30 Two potential ways to avoid immune rejection of ES cells 1. Somatic cell nuclear transfer—use a nucleus from one of the patient’s own cells and transfer it into an unfertilized egg to develop an embryo from which ES cells can be harvested Embryonic stem cells without making embryo 2. Treat some of the patient’s own cells with factor known to specify ES cell character (e.g. a combination of Oct3/4, Sox2, Myc and Klf4 can convert differentiated cells into cells with ES cell characteristics) 31 31 Continual renewal is important for maintaining all structures Tissues often renew themselves naturally, but when they can’t medical treatments can be used 32 32 Lecture 6 reading 1419-1423 1430-1433 1454-1459 1476-1482 33 33 ...
View Full Document

This note was uploaded on 04/03/2012 for the course BIOLOGY BIO230 taught by Professor Harris during the Fall '11 term at University of Toronto.

Ask a homework question - tutors are online