Ch.20 - Tissues, Stem Cells, Cancer Flashcards
20A - ECM, CT 20B - Epithelial Sheets, Cell Junctions 20C - Tissues Maintenance and Renewal 20D - Cancer
Summarize the general diffs b/w animal and plant tissue, partic wrt ECM.
Plants are sedentary: tissues are mostly rigid, although cells are weak/fragile if isolated fr ECM/cell wall.
- Cell wall is a boxlike structure that encloses, protects, and constrains the shape of cells.
- Common principle of tissue construction: many tiny cells attached t/g via CJs.
Animal tissues are more diverse.
- Cells/ECM are orgz in many diff ways: some tissues (bone, tendon) have abundant ECM, others (muscle, epidermis) have scant ECM → cytoskeletons themselves carry mechanical load.
T/F: Plant cell cytoskeletons lack intermediate filaments.
True
Plant cell cytoskeletons lack tension-bearing ifils found in animal cells → have virtually no tensile strength of their own, i.e. rely almost entirely on cell wall for mech strength.
T/F: all cell walls are tough and rigid.
False
Cell wall is tough, but not always rigid: provides turgor pressure during osmotic swelling → forms semirigid tissue, e.g. a crisp lettuce leaf.
- If water is lacking → cells shrink → leaf wilts.
Summarize the formation of three types of cell walls.
Most newly formed cells initially make relatively thin primary cell walls → slowly expand (via osmotic swelling; turgor pressure) to accommodate cell growth.
A more rigid secondary cell wall is typ produced once cell growth stops—either by thickening of primary wall or by deposition of new layers w diff composition underneath.
Specialized cell walls form when plant cells become specialized, e.g. waxy, waterproof walls for surface epidermal cells of a leaf; hard, thick, woody walls for xylem cells of a stem; etc.
Like all ECMs, plant cell walls derive tensile strength fr ____ (long/short) fibers oriented ______ (along/perpendicular to) lines of stress.
Like all ECMs, plant cell walls derive tensile strength fr long fibers oriented along lines of stress.
In higher plants, long fibers of the cell wall are typ made fr _______, a type of _________.
In higher plants, long fibers of the cell wall are typ made fr cellulose, a type of polysaccharide.
- E.g. woody tissue: highly cross-linked network of lignin (complex polymer of aromatic alcohol groups) is deposited w/i this matrix to make it more rigid and waterproof.
For plant cell to grow/change shape, cell wall must stretch/deform. Describe how cellulose microfibrils govern the orientation of growth.
Cellulose microfibrils resist stretching → orientation governs direction in wh growing cell enlarges.
- I.e. turgor pressure is uniform in all directions → cell will elongate in direction perpendicular to orientation of microfibrils.
- E.g. if arranged circumferentially → grows more readily in length than girth.
Cellulose is produced in radically diff way fr most other ECM components, wh are typ synth’d inside cell and exported by exocytosis. Explain how cellulose production differs.
Cellulose is synthd by enzymes embedded in pmem (cellulose synthase complex), wh xprt sugar monomers across pmem (in → out) and incorporate into set of growing polymer chains at their points of mem attachment on EC surface.
- Ea set of chains assembles to form a cellulose microfibril.
- Enzyme complexes move in mem → lay down trail of oriented cellulose microfibrils behind them.
Cellulose synthase complex moves laterally in pmem and lays down a trail of oriented cellulose microfibrils. What guides the path of this enzyme and thus controls plant cell shape/tissue modeling?
Path of enzyme complex is guided by mtubs just beneath pmem that are aligned exactly w EC cellulose microfibrils; i.e. serve as tracks for enzyme movement.
- Thus, cytoskeleton controls shape of plant cell and modeling of tissues.
Cells in the stem of a seedling grown in the dark orient their mtubs horizontally. How would you expect this to affect growth?
Horizontal mtub orientation → horizontal cellulose microfibril orientation (deposited in cell walls) → vertical plant growth.
What are the four major types of tissues in animals? Wh type of tissue has distinct architecture?
Four major types of tissues in animals: connective, epithelial, nervous, and muscular; w conn tissue (CT) having distinct architecture.
- In CT, ECM is plentiful and carries mechanical load; in other tissues, ECM is scant and cells are directly joined t/g and carry mech load thru cytoskeleton.
Animal CTs are enormously varied: can be tough/flexible (tendons, dermis), hard/dense (bone), resilient/shock-absorbing (cartilage), or soft/transparent (vitreous humor of eye).
Regardless, bulk of tissue is _______. In all CT, tensile strength—whether great or small—is chiefly provided by ________.
Animal CTs are enormously varied: can be tough/flexible (tendons, dermis), hard/dense (bone), resilient/shock-absorbing (cartilage), or soft/transparent (vitreous humor of eye).
Regardless, bulk of tissue is ECM. In all CT, tensile strength—whether great or small—is chiefly provided by collagen (a fibrous protein).
- Various types of collagen (and interwoven molecules) → various types of CT.
- E.g. elastin is interwoven w collagen of ECM of arterial walls → provide flexible resilience as blood pulses thru.
________ provides tensile strength in animal CT.
Collagen provides tensile strength in animal CT.
- Long, stiff, triple-helical structure of collage polypeptide chains.
- Collagen fibrils are ordered polymers of collagen → can pack into still thicker collagen fibers.
- Other types of collagen decorate the surface of collagen fibrils and link fibrils t/g and to other components in ECM.
Mutations in genes encoding collagens are often detrimental, partic those that effect glycines, wh are reqd at every third position in collagen polyp chain to assemble into triple-helical rod.
Would you expect collagen mutations to be detrimental if only one of the two copies of a collagen gene is defective?
As three collagen chains have to come t/g to form triple helix, a defective molecule will impair assembly, even if normal collagen chains are present at same time. Therefore, collagen mutations are dominant; that is, they have a deleterious effect even in presence of a normal copy of the gene.
Mutations in genes encoding collagens are often detrimental, partic those that effect glycines, wh are reqd at every third position in collagen polyp chain to assemble into triple-helical rod.
A puzzling observation is that the change of a glycine residue into another AA is most detrimental if it occurs toward amino terminus of the rod-forming domain. Suggest an explanation.
Diff severity of mutations results fr polarity in assembly process. Collagen monomers assemble into triple-helical rod starting fr their amino-terminal ends. A mutation in an “early” glycine therefore allows only short rods to form, whereas a mutation farther downstream allows for longer, more normal rods.
CT cells that manufacture/inhabit ECM are named according to tissue, such as _________ in skin/tendon/other CTs and _________ in bone.
CT cells that manufacture/inhabit ECM are named according to tissue, such as fibroblasts in skin/tendon/other CTs and osteoblasts in bone.
Fibro/osteoblasts synth collagen, in its precursor form, as well as other macromolecules of ECM → secreted → assemble into huge, cohesive aggregates.
Describe the precursor form of collagen, and what would happen if collagen was instead synth’d directly.
Fibro/osteoblasts synth collagen, in its precursor form of procollagen, as well as other macromolecules of ECM → secreted → assemble into huge, cohesive aggregates.
- Procollagens contain unstructured extensions at ea end that obstruct premature assembly into collagen fibrils → secreted → emerge into EC space → procollagen proteinases cleave extensions to enable assembly.
- If collagen was synthd directly, assembly would occur before secretion → cell would become choked w own products.
For tissues to grow, repair, and renew cells, or to allow migratory cells (e.g. macrophages) to burrow thru, tissue cells must also degrade ECM, often thru __________ (enzyme).
For tissues to grow, repair, and renew cells, or to allow migratory cells (e.g. macrophages) to burrow thru, tissue cells must also degrade ECM, often thru matrix proteases.
- Also play part in many disease processes, e.g. arthritis (break down cartilage) and cancer (help cancer cells invade normal tissue).
Orientation of collagen fibrils fits function and is det by CT cells that synth collagen. Describe how fibril orientation fits function in skin vs tendons.
Skin - fibrils are woven in wickerwork pattern, or in alt layers w diff orientations so as to resist tensile stress in multiple directions.
Tendons (muscle to bone) - fibrils are aligned in parallel bundles along major axis of tension.
Fibroblasts influence alignment of collagen fibers, and collagen fibers in turn affect distribution of fibroblasts. Explain.
Fibro/osteoblasts first deposit collagen in an oriented fashion, then rearrange. I.e. during tissue dev, fibroblasts secrete collagen then crawl over and pull on it → compact it into sheets and draw it out into cables.
________ are xmem receptor proteins that couple the ECM to the cytoskeleton, while ______ are ECM proteins that provide linkage to collagen.
Integrins are xmem receptor proteins that couple ECM to cytoskeleton, while fibronectins are ECM proteins that provide linkage to collagen.
- Cells do not attach well to bare collagen; req linkage via fibronectin.
Formation/breakage of attachments on either end of integrin enable cell to crawl thru tissue → attach ECM at its front end and releasing its grip at rear.
Describe how integrins coord cell movement thru signif conform changes.
Integrin’s EC domain binds fibronectin → IC domain binds (thru set of adaptor molecules) to mfil (actin).
Binding fibronectin (and EC collagen) causes integrin to stretch out into an extended, activated state → can latch onto actin on IC side, and vice-versa.
- I.e. IC signal can activate integrin fr cytosolic side → integrin extends/attaches EC struc, e.g. collagen. Likewise, binding an EC structure can activate IC signal paths (e.g. protein kinases) that assoc w IC side of integrin.
Collagen provides tensile strength (resists stretching), but _________________ resist compression.
Collagen provides tensile strength (resists stretching); glycosaminoglycans (GAGs) resist compression.
- Neg charged polysacch chains.
- Covalently link to ECM proteins → proteoglycan.
-
Strongly hphilic → osmotically active: attract cations (Na+) and form extended conforms → high volume-to-mass ratio, i.e. “space-fillers”.
- Swelling pressure counterbalanced by tension fr interwoven collagen fibers.
- GAG-to-Collagen ratio is small in dense, compact tissue (tendon, bone) and high in jelly-like tissue (aqeous humor).
- Proteoglycans also bind secreted EC signals and regulate their passage thru ECM; imp in cell differentiation.
GAGs are _____ (neg/pos) charged ________ (polysacch/polypep) chains made of repeating ______ (disacch/di-peptide) units; typ ________ (non/covalently) linked to core proteins to form ________, wh are v diverse in size, shape, and chemistry.
GAGs are negatively charged polysacch chains made of repeating disacch units; typ covalently linked to core proteins to form proteoglycans, wh are v diverse in size, shape, and chemistry.
- Typ, many GAG chains are attached to single core protein → linked at one end to another GAG, creating enormous aggregate resembling a bottlebrush.
In wh type of tissues are glycosaminoglycans (GAGs) more abundant: bone or the aqueous humor of the eye?
GAGs are more abundant in aqueous humor.
- Typ, GAGs are strongly hphilic and tend to adopt highly extended conforms → occupy huge volume relative to mass → “space fillers” in ECM of CTs.
- In dense, compact CTs (tendon, bone), proportion of GAGs is small, ECM consists almost entirely of collagen (or, collagen w Ca2+-Phos crystals in bone).
- In jelly-like humor in interior of eye, abundant GAG (plus water) and only small amount of collagen.
Even at v low concens, GAGs form hphilic gels: multiple neg charges attract cloud of cations (chiefly Na+) that are osmotically active, i.e. draw large amount of water to ECM → swelling pressure → balanced via tension in collagen fibers interwoven w proteoglycans.
In what type of tissue might an ECM rich in collagen and a large qty of GAGs be desireable?
In tough, resilient, compression-resistant CT (cartilage matrix of knee joint), ECM is rich in collagen w large qty of GAGs trapped in meshwork → enormous swelling pressure and counterbalancing tension.
Proteoglycans are characterized by the abundance of negative charges on their sugar chains. How would these props differ if negative charges were not as abundant?
The remarkable ability to swell and thus occupy a large volume of space deps on negative charges, wh attract a cloud of cations (chiefly Na+) → draw in large amounts of water (via osmosis) → give proteoglycans unique props.
Uncharged polysacchs such as cellulose, starch, and glycogen, by contrast, are easily compacted into fibers or granules.
_______ are sheets in wh cells are joined t/g side-to-side; may be many cells thick (stratified, e.g. epidermis) or only one cell thick (gut lining).
Epithelia are sheets in wh cells are joined t/g side-to-side; may be many cells thick (stratified, e.g. epidermis) or only one cell thick (gut lining).
- Many forms: tall (columnar), squat (cuboidal), or fat (squamous).
T/F: w/i a given sheet, all epithelial cells are of the same type.
False
W/i given sheet, cells may be all the same type or a mix.
- Functions vary: some protect, some secrete specialized products (hormones, milk, tears), absorb nutrients (e.g. gut lining), or detect signals (e.g. photoreceptors, hair cells).
Epithelial sheets are ______ (non/polarized) and rest on a ___________.
Epithelial sheets are polarized and rest on a basal lamina.
- An epithelial sheet has two faces: apical surface is free/exposed to EC space (air/watery fluid); basal surface is attached to a sheet CT (basal lamina).
The basal lamina consists of a thin, tough sheet of _______, composed mainly of ________ and ________ (both proteins).
The basal lamina consists of a thin, tough sheet of ECM, composed mainly of type IV collagen and laminin.
- Like fibronectin in other CTs, laminin provides linkage sites for integrins in basal pmems of epithelial cells, i.e. act as cell junction.
- Recall: integrins don’t attach well to bare collagen; req linkage proteins.
The simple columnar epithelium that lines the small intestine consists of two intermingled cell types: absorptive cells and goblet cells, both of wh are polarized. Describe how chemically diff faces of such a tissue det its function.
Absorptive cells import nutrients fr gut lumen thru apical surface → export fr basal surface into underlying tissues.
- Often called “brush-border” cells bc of mass of microvilli on apical surface, wh ↑ absorptive area.
Goblet cells synth mucus (protects/lubricates gut lining) → discharge fr apical end only; Golgi , secretory vesicles, and cytoskeleton are all polarized.
- Shape and name derive fr mass of secretory vesicle that distends cytoplasm in apical region.
Polarity deps on junctions that cells form w one/an and w basal lamina → in turn, control arrangement of an elaborate sys of mem-assoc IC proteins that create polarized orgz of cytoplasm.
_______ junctions make an epithelium leak-proof and separate its apical/basal surfaces.
Tight junctions make an epithelium leak-proof and separate its apical/basal surfaces.
T/F: most epithelia contain all types of cell junctions.
True
Most epithelia incl all types CJs, ea characterized by its own class of mem proteins.
- Functionally classified: some provide seal (tight junctions), some provide mech attachements; some provide special type of intimate chem comm.
Tight junctions, wh act as seals in vertebrates, are formed fr ______ and ______ (proteins), ea wh binding to ____ (same/diff) type in apposed mem.
Tight junctions, wh act as seals in vertebrates, are formed fr claudins and occludins, ea wh binding to same type in apposed mem, i.e. claudin-claudin (“homophilic binding”).
Describe two ways that tight junctions help maintain polarity of individual epithelial cells.
Tight juncs around apical region of ea cell prevents diffusion of proteins w/i pmem → keeps apical domain diff fr basal (or basolateral) domain.
In many epithelia, tight CJs are sites of assembly for complexes of IC proteins that govern apico-basal polarity.
_________ junctions bind epithelial cells robustly to one/an and to basal lamina.
Cytoskeleton-linked (anchoring) junctions bind epithelial cells robustly to one/an and to basal lamina.
- Three types: adherens junctions, desmosomes, hemidesmosomes.
Describe the general mechanism of anchoring cell junctions.
Cell adhesion proteins span pmem → link cytoskeletal fils inside cell. In this way, cytoskeletal fils are tied into a network that extends fr cell-to-cell across whole expanse of epithelial sheet.
Adherens junctions and desmosomes are built around _______ (peripheral/xmem) _______________ (protein type), wh extend into EC space to bind identical protein in pmem of apposed cells, and, internally, attach via linker proteins to either _____ (e.g. adherens) or ______ (e.g. desmos).
Adherens junctions and desmosomes are built around xmem calcium-dep adherence proteins (cadherins), wh extend into EC space to bind identical caderins in pmem of apposed cells, and, internally, attach via linker proteins to either actin fils (e.g. adherens) or keratin ifils (e.g. desmos).
- Cadherins req Ca2+ to be present in EC space, hence the name.
Adherens juncs form adhesion belts around circumference of cell, in wh a contractile bundle of _______ runs along the _________ (non/cytoplasmic) surface of pmem near _____ (apical/basal) end, just below tight junction → link to ________ via several linker proteins → link to identical proteins in apposed cells.
Adherens juncs form adhesion belts around circumference of cell, in wh a contractile bundle of actin fils runs along the cytoplasmic surface of pmem near apex/apical end, just below tight junction → link to cadherin via several linker proteins → link to identical cadherin in apposed cells.
Actin filaments can contract. What effect does this have on epithelial sheets?
Actin fils can contract → epithelial sheet can dev tension and signif change shape.
- Can shrink apical surface along one axis → sheet rolls itself into a tube, e.g. creation of neural tube → CNS.
- Can shrink apical surface along all axes at once → sheet can invaginate → create spherical vesicle by pinching off fr rest of epithelium, e.g. creation of lens vesicle → lens of eye.
Desmosomes consist of a dense ________ composed of IC linker proteins that bind a bundle of _________ on its cytoplasmic surface and binds _____ (heads/tails) of xmem ________ on opp face (against pmem), whose EC domain then interacts w identical domains of proteins in adj cell pmems → hold cells t/g.
Desmosomes consist of a dense plaques composed of IC linker proteins that bind a bundle of keratin ifils on its cytoplasmic surface and binds tails of xmem cadherins on opp face (against pmem) → cadherin’s EC domain interacts w identical domains of proteins in adj cell pmems → hold cells t/g.
- Recall: ifils = signif tensile strength, e.g. skin epidermis.
Hemidesmosomes anchor ________ to ________ via xmem _________ (cell adhesion molecule) in _____ (apical/basal) pmem.
Hemidesmosomes anchor keratin ifils to basal lamina via xmem integrins (cell adhesion molecule) in basal pmem.
- EC domains of integrins bind to laminin in basal lamina; IC domains (tails) link to keratin ifils; looks like half a desmo, hence the name.
- Blisters are a painful reminder that it isn’t enough for epidermal cells to be firmly attached to one another; must also anchor to underlying CT.
___________ are communicating CJs found in virtually all epithelia/many other types of animal tissue; allow cytosolic _______ and _______ to pass fr cell to cell.
Gap junctions are communicating CJs found in virtually all epithelia/many other types of animal tissue; allow cytosolic inorganic ions and small molecules to pass fr cell to cell.
Gap junctions are composed of xmem, ring-like protein complexes called _______, wh align _______ (side-by-side/end-to-end) w _____ (same/diff) type of protein in apposed cell.
Gap junctions are composed of xmem, ring-like protein complexes called connexons, wh align end-to-end w another connexon in apposed cell to form aqueous channel.
- Thus, creates an electrical and metabolic coupling b/w cells; e.g. cardiac muscle cells.
Summarize the main types of cell junctions.
See fig
T/F: Plant tissues lack tight junctions, adherens junctions, hemi/desmosomes, and gap junctions.
True
Plant tissues lack tight junctions, adherens junctions, hemi/desmosomes, and gap junctions; h/e, have diff type of comm CJ: plasmodesmata.
How are plasmodesmata diff than gap junctions?
Unlike gap junctions, plasmodesmata form cytoplasmic channels lined w pmem, i.e. plant cells are essentially continuous w one/an.
- Channel also typ contains a desmotubule: a fine tubular struc derived fr smooth ER.
- Inorganic small molecules, and even macromolecules—incl some proteins and regulatory RNAs—can pass thru plasmodesmata.
- Thus, controlled traffic of xcr regulators and regulatory RNAs fr one cell to another is imp in plant dev.
Gap junctions are dynamic structures that, like conventional ion channels, are gated: close by reversible conform change in response to IC signal. Permeability of gap junctions ↓ w/i seconds, such as when IC [Ca2+] ↑. Speculate why this form of regulation might be imp for tissue health.
Suppose a cell is damaged so that its pmem becomes leaky. Ions present in high concen in ECF (Na+, Ca2+) rush into cell, and valuable metabolites leak out.
If cell were to remain connected to its healthy neighbors, these too would suffer fr the damage. But Ca2+ influx causes the damaged cell’s gap junctions to close immediately → effectively isolates cell.
Although specialized tissues differ in many ways, all have certain basic reqs, typ provided for by a mix of cell types.
Describe the common characteristics.
All tissues need mechanical strength, often supplied by framework of CT inhabited by fibroblasts.
Most tissues are innervated by nerve-cell axons ensheathed by Schwann cells (myelination → elec insulation).
Macrophages dispose of dead/damaged cells and other unwanted debris, and lymphocytes/other WBCs combat infection.
Most cell types originate outside the tissue and invade it, either early in course of dev (endothelial cells, nerve-cell axons, and Schwann cells) or continually during life (macrophages/WBCs).
Most specialized cells that need continual replacement are themselves unable to divide, i.e. terminally differentiated, e.g. RBCs, epidermal cells on skin surface, and absorptive/goblet cells of gut epithelium.
Describe how these cells are continually replaced.
Typ dev fr stock of non-differentiated, proliferating precursor cells that divide a limited # of times before they terminally differentiate.
Precursor cells are themselves typ derived fr a much smaller # of self-renewing, non-differentiated stem cells.
- Unlike precursor cells, stem cells can divide w/o limit (or at least thru/o org’s lifetime).
- Stem-CDs either prod two stem cells or two precursor cells.
The job of stem/precursor cells is not to carry out specialized function of differentiated cells, but rather to produce cells that will.
T/F: stem cells and precursor cells are both non-differentiated and can only divide a limited # of times before becoming terminally differentiated.
False
Both are non-differentiated, but, unlike precursor cells, stem cells can divide w/o limit (or at least thru/o org’s lifetime).
Stem-cell divisions either prod two _________ cells or two ________ cells, as long as pool of stem cells is maintained.
Stem-cell divisions either prod two prolif precursor cells or two stem cells, as long as pool of stem cells is maintained.
In the lining of the small intestine, absorptive/secretory (e.g. goblet) cells are arranged as single-layered, simple epithelium covering surfaces of finger-like villi that project into gut lumen → continuous w epithelium lining the crypts, wh descend into underlying CT.
Describe the continuous process of replacing terminally differentiated absorptive and secretory cells.
Stem cells lie near bottom of crypts → divide mostly into prolif precursor cells → move upward in plane of epithelial sheet, terminally differentiating into absorptive/secretory cells → shed into gut lumen and die when they reach tips of villi.
- Note: besides mucus-secreting goblet cells, gut lining also contain smaller #s of secretory enteroendocrine cells (hormones) and Paneth cells (antibacterial proteins).
- Stems cells also divide directly into terminally differentiated Paneth cells, wh remain at bottom of crypt; i.e. don’t divide first into prolif precursor cells.
As a contrasting example to the continuous replacement of absorptive/secretory cells in the gut lining, stem/prolif precursor cells are confined to the basal layer beneath the stratified epithelium of the epidermis → adhere to basal lamina.
Describe the continuous process of replacing terminally differentiated cells in the epidermis.
Prolif precursor cells emerge fr basal layer and stop dividing → move outward, perpendicular to plane of cell sheet, differentiating as they go → terminally differentiated cells (and their corpses) are eventually shed fr skin surface.
Epidermal cells undergo a special form of cell death: nucleus and other organelles disintegrate, and cell shrinks to form of a flattened scale, packed w keratin fils (ifils) → scales shed fr skin surface.
T/F: stem cells are specific to their differentiated progeny, i.e. a single type of stem cell can only give rise to one type of differentiated progeny.
False
A single type of stem cell gives rise to several types of differentiated progeny.
- Intestinal stem cells prod absorptive cells, goblet (mucus) cells, and several other secretory cell types (e.g. enteroendocrine, Paneth).
- All diff cell types in blood—both RBCs that carry oxygen and many types of WBCs that fight infection—ultimately derive fr a shared hemopoietic stem cell found in bone marrow.
________ proteins are a class of signals that promote prolif of stem cells and precursor cells at base of intestinal crypt
Wnt proteins are a class of signals that promote prolif of stem cells and precursor cells at base of intestinal crypt.
In the Wnt signaling path in the gut lining, Wnt’s are secreted by cells in/around the ______ base, partic by _______ cells, wh are generated fr gut ______ cells but remain at the bottom of the ______.
In the Wnt signaling path in the gut lining, Wnt’s are secreted by cells in/around crypt base, partic by Paneth cells, wh are generated fr gut stem cells but remain at bottom of crypt.
- Paneth cells secrete antimicrobial peptides as well as provide signals to sustain stem-cell population fr wh they themselves derive.
- Crypt cells produce signals that act at longer range to prevent activation of Wnt pathway outside crypts.
- Crypt cell also exchange signals to control their diversification → some differentiate into secretory cells, others become absorptive cells.
________ stem cells have been derived fr inner cell mass of early mouse embryos and maintained indefinitely as ________ stem cells in culture.
Embryonic stem cells (ES cells) have been derived fr inner cell mass of early mouse embryos and maintained indefinitely as pluripotent stem cells in culture.
- Cells fr culture dish put back into early embryo → can give rise to all tissues/cell types in body, incl germ cells.
- Descendants of pluripotent ES cells—now in the embryo—can integrate perfectly into whatever site they come to occupy, i.e. adopt same character/behavior that normal cells would show at that site.
Progeny of pluripotent ES cells can also be induced to differentiate in culture into many diff cell types when provided w approp ___________.
Progeny of pluripotent ES cells can also be induced to differentiate in culture into many diff cell types when provided w approp EC signals.
A _______ is simply a set of cells/individuals that are essentially genetically identical, by virtue of descent fr single ancestor cell.
A clone is simply a set of cells/individuals that are essentially genetically identical, by virtue of descent fr single ancestor cell.
___________ is cloning of entire multicellular organisms.
Reproductive cloning is cloning of entire multicellular organisms.
- In reprod cloning, the need for two parents and sexual union is bypassed.
- Demonstrated in mice/sheep/other domestic animals via nuclear transplantation.
Describe the process of nuclear transplantation, as used in reproductive cloning.
Begins w unfertilized (haploid) egg cell → nucleus sucked out/destroyed and replaced w regular, diploid nucleus of taken fr adult tissue → hybrid cell devs in culture for a few days.
Hybrid cell gives rise to early embryo (blastocyst) containing ~200 cells → xfrd into uterus of foster mother → dev continues as it would in a normal embryo.
- Org is genetically identical to adult who donated diploid nucleus (except for small amount of GI in mito, wh are inherited w egg cytoplasm).
How does therapeutic cloning differ fr reproductive cloning?
Therapeutic cloning uses nuclear transplantation to prod cultured, personalized ES cells w the aim of generating various cell types that can be used for tissue repair/disease studies.
- Cells obtained are genetically almost identical to original donor cell → can be grafted back into adult fr whom the donor nucleus was taken, thereby minimizing immunological rejection.
Problems assoc w therapeutic cloning—prod of personalized ES cells by nuclear transplantation—can now be bypassed by an alt method. Explain.
Cells taken fr adult tissue → grown in culture → reprogrammed into ES-like state by artificially driving expr of a set of three xcr regulators: Oct3/4, Sox2, Klf4.
Can convert fibroblasts into induced pluripotent stem cells (iPS cells), wh have nearly all props of ES cells, incl ability to prolif indefinitely and differentiate in diverse ways and to contrib to any tissue.
Conversion rate is low—only tiny proportion of fibroblasts make the switch—and there are serious worries about safety of implanting into humans derivatives of cells w such an abnormal dev history.
What two heritable properties define cancer cells?
Cancer cells are defined by two heritable props: they and their progeny (1) prolif in defiance of normal constraints and (2) invade/colonize territories normally reserved for other cells; combo of wh is lethal.
- Cells that have the first property but not the second prolif excessively but remain clustered t/g in a single mass → benign tumor, wh can typ be removed cleanly/completely by surgery.
- Malignant tumors are those whose can invade surrounding tissue: cells often break loose fr primary tumor and enter bloodstream or lymphatic vessels → form secondary tumors (metastases) at other sites.
Most human cancer cells not only contain many mutations, but are also genetically unstable. What does this mean?
Most human cancer cells not only contain many mutations, but are also genetically unstable, wh results fr mutations that interfere w accurate repl/repair of genome and thereby ↑ mutation rate itself.
- ↑ mutation rate sometimes results fr a defect in one of the many proteins reqd involved in DNA repl/repair.
- Sometimes, there may be a defect in cell-cycle checkpoint mechanisms.
- Sometimes, there may be a fault in machinery of mitosis → chromo damage, loss, or gain.
Cancerous mutations do not cripple the mutant cells; instead, provide increasingly competitive advantage. Explain how this is achieved and its implication on treatment.
Tumorsevolve by repeated rounds of mutation,prolif, and natural selection.
Initial population of mutant cells grows → slowly evolves and devs new, sometimes favorable chance mutations, i.e. enhance prolif/survival of cancerous cells.
- Some cancers contain multiple malignant clones, ea w own collection of mutations, in addition to common set of mutations that reflect tumor’s origin fr a founding mutant cell.
T/F: cells must acquire many abnormal properties before becoming cancerous.
True
Cancerous cells must acquire many abnormal props.
E.g. a prolif precursor cell in gut lining must be altered to continue dividing after normal signals cease → must also avoid cell death, displace normal neighbors, and attract blood supply to nourish continued tumor growth.
- For (benign) tumor cells to become invasive (malignant), must detach fr epithelial sheet and digest thru basal lamina into underlying CT.
- To form metastases, must enter/exit blood/lymph vessels and settle, survive/prolif in new sites.
For many cancer-critical genes, danger results fr creating hyperactive proteins thru what are called ___________ mutations, wh are typ _________ (dominant/recessive).
For many cancer-critical genes, danger results fr creating hyperactive proteins thru what are called gain-of-function mutations, wh are typ dominant: only one gene copy needs to be mutated to cause trouble.
Gain-of-function mutations are typ dominant: only one gene copy needs to be mutated to cause trouble. This resulting mutant gene is called the _________, while the corresponding normal form is called the ___________.
Gain-of-function mutations are typ dominant: only one gene copy needs to be mutated to cause trouble. This resulting mutant gene is called the oncogene, while the corresponding normal form is called the proto-oncogene.
- Proto-oncogenes can be converted into oncogenes in many ways.
For some cancer-critical genes, such as ____________ genes, the danger lies in mutations that destroy activity. These mutations are called ___________ mutations, wh are typ __________ (dominant/recessive).
For some cancer-critical genes, such as tumor suppressor genes, the danger lies in mutations that destroy activity. These mutations are called loss-of-function mutations, wh are typ recessive: both gene copies must be lost/inactivated.
- Tumor suppressor genes can also be silenced by epigenetic changes, wh alter gene expr w/o changing nt seq.
- Epigenetic changes are thought to silence some tumor suppressor genes in most human cancers.
__________ changes are thought to silence some tumor suppressor genes in most human cancers.
Epigenetic changes are thought to silence some tumor suppressor genes in most human cancers
Genes that are critical for cancer are classified as ___________ or ___________, according to whether the dangerous mutations are _________ or _________.
Genes that are critical for cancer are classified as proto-oncogenes or tumor suppressor genes, according to whether the dangerous mutations are dominant or recessive.
Mutated genes often fall into small # of key regulatory pathways, such as?
Mutated genes often fall into small # of key regulatory pathways: those that govern initiation of cell prolif, control cell growth, and regulate cell’s response to DNA damage/stress.
- E.g. in almost every case of glioblastoma (most common human brain tumor), mutations disrupt all three of these fundamental pathways.
Explain how some families are exceptionally prone to certain types of cancer.
May inherit one mutant and one normal tumor suppressor gene copy → sufficient for normal cell behavior (recall: loss-of-function; recessive), but all cells are only one mutational step away fr total loss of gene’s function.
- Individual tumors arise fr cells w somatic mutation that inactivates the one remaining normal gene copy.
- Thus, # of new mutations reqd is smaller → early onset of disease.
- E.g. colorectal cancer: dev of polyps traced to deletion/inactivation of Adenomatous Polyposis Coli (APC), a tumor suppressor gene.
