Cours Medecine Info Histologie 2 Voies Aeriennes Intestin

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    Vie et mort des cellules dans les tissus

    I. L'piderme et son renouvellement par les cellulessouches

    II. pithlium sensorielIII. Voies ariennes et intestinIV. Vaisseaux sanguins et cellules endothlialesV. Renouvellement par des cellules souches

    multipotentes : la formation des cellules sanguinesVI. Gense : modulation et rgnration du musclesquelettiqueVII. Les fibroblastes et leurs transformations : la famille

    des cellules du tissu conjonctifVIII. Ingnierie des cellules souches

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    Vie et mort des cellules dans les tissus

    tre unicellulaire : individu originel

    tre pluricellulaire : cellules auservice du corps tout entier Plus de 200 types de cellules

    diffrents dans lorganisme

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    Cells of the Adult HumanBody : a Catalogue

    How many distinct cell types are there in an adult human being? In other words, how many

    normal adult ways are there of expressing the human genome? A large textbook of histologywill mention about 200 cell types that qualify for individual names. These traditional names arenot, like the names of colors, labels for parts of a continuum that has been subdividedarbitrarily: they represent, for the most part, discrete and distinctly different categories. Withina given category there is often some variationthe skeletal muscle fibers that move the eyeballare small, while those that move the leg are big; auditory hair cells in different parts of the earmay be tuned to different frequencies of sound; and so on. But there is no continuum of adultcell types intermediate in character between, say, the muscle cell and the auditory hair cell.

    The traditional histological classification is based on the shape and structure of the cell as seen

    in the microscope and on its chemical nature as assessed very crudely from its affinities forvarious stains. Subtler methods reveal new subdivisions within the traditional classification.Thus modern immunology has shown that the old category of lymphocyte includes more than10 quite distinct cell types. Similarly, pharmacological and physiological tests reveal that thereare many varieties of smooth muscle cellthose in the wall of the uterus, for example, arehighly sensitive to estrogen, and in the later stages of pregnancy to oxytocin, while those in thewall of the gut are not. Another major type of diversity is revealed by embryologicalexperiments of the sort discussed in Chapter 21. These show that, in many cases, apparentlysimilar cells from different regions of the body are nonequivalent, that is, they are inherentlydifferent in their developmental capacities and in their effects on other cells. Thus, withincategories such as fibroblast there are probably many distinct cell types, different chemicallyin ways that are not easy to perceive directly.

    For these reasons any classification of the cell types in the body must be somewhat arbitrarywith respect to the fineness of its subdivisions. Here, we list only the adult human cell typesthat a histology text would recognize to be different, grouped into families roughly according tofunction. We have not attempted to subdivide the class of neurons of the central nervoussystem. Also, where a single cell type such as the keratinocyte is conventionally given asuccession of different names as it matures, we give only two entriesone for thedifferentiating cell and one for the stem cell. With these serious provisos, the 210 varieties of

    cells in the catalogue represent a more or less exhaustive list of the distinctive ways in which agiven mammalian genome can be expressed in the phenotype of a normal cell of the adultbod .

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    http://www.garlandscience.com/textbooks/0815332181/pdfs/appe

    ndix.pdfp://www.garlandscience.com/textbooks/0815332181/pdfs/appendix.pdf

    http://www.garlandscience.com/textbooks/0815332181/pdfs/appendix.pdfhttp://www.garlandscience.com/textbooks/0815332181/pdfs/appendix.pdfhttp://www.garlandscience.com/textbooks/0815332181/pdfs/appendix.pdfhttp://www.garlandscience.com/textbooks/0815332181/pdfs/appendix.pdfhttp://www.garlandscience.com/textbooks/0815332181/pdfs/appendix.pdfhttp://www.garlandscience.com/textbooks/0815332181/pdfs/appendix.pdf
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    Tissu Association de ces types cellulairesqui collaborent entre elles

    Forment des organes

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    Consquences du contrle de lexpression des gnes etdes mcanismes du dveloppement animal

    Cration de la diversification cellulaire dans lembryonpar des mcanismes gntiques molculaires

    Maintien de la diversification des cellules grce audialogue et la mmoire des cellules

    Construction des tissus par la matrice extra cellulaire

    Mode de vie des cellules spcialises

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    Questions poses

    Comment les cellules collaborent entreelles pour excuter leur tche ?

    Comment naissent vivent et meurentles nouvelles cellules spcialises ?

    Comment est prserve larchitecture

    des nouveaux tissus malgr leurperptuel remaniement ?

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    Rponses diverses Exemples illustrant les principes

    gnraux Intressants par loriginalit de leurs

    moyens dtude

    Nombreux problmes non rsolus

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    Plan

    I. L'piderme et son renouvellement par les cellulessouches

    II. pithlium sensorielIII. Voies ariennes et intestin

    IV. Vaisseaux sanguins et cellules endothlialesV. Renouvellement par des cellules souches

    multipotentes : la formation des cellules sanguinesVI. Gense : modulation et rgnration du muscle

    squelettiqueVII. Les fibroblastes et leurs transformations : la familledes cellules du tissu conjonctif

    VIII. Ingnierie des cellules souches

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    Embryon

    3 feuilletsEctoblaste :

    I (piderme) II (pithliums sensoriels)

    Msoblaste

    Entoblaste

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    Ectoblaste

    Nombreuses varits de tissus Spcialisations trs diffrentes

    Modes de vie diffrents

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    Entoblaste

    Couche interne de lembryon Tube digestif primitif

    Un vritable zoo de types cellulairesqui bordent le tube digestif et sesannexes

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    Plan

    1. Respiratoire2. Tube digestif

    3. Foie

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    2 Tube digestif

    Tous les vertbrs nont pas despoumons

    Mais tous (et les invertbrs aussi) ontun tube digestif

    Cellules spcialises dans la digestion de nourriture et labsorption des molcules nutritives

    Mais ne peuvent pas fonctionner enmme temps : il ne faut pas digrer letube digestif

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    Organisation de la digestion

    Dans un lieu spar : lestomac Hydrolyse acide Actions enzymatiques

    Passage dans lintestin grle Absorption Poursuite de la digestion ( pH neutre)

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    Types cellulaires

    Estomac Cellules qui scrtent lacide Cellules qui scrtent les enzymes pH acide Cellules mucus

    Glandes (comme le pancras) Cellules qui scrtent bicarbonates pour neutraliser lacide Cellules qui scrtent des enzymes digestives

    Intestin

    Cellules absorbantes Cellules qui scrtent le manteau de mucus

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    Mesure supplmentaire de

    protection Renouvellement continu de lpithlium Turnover dune semaine ou moins

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    Renouvellement dans

    lintestin grle pithlium simple recouvrant Les villosits qui svaginent Les cryptes qui sinvaginent dans le tissu

    conjonctif sous-jacent

    R ll t d

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    Fig 22-19 A

    Renouvellement durevtement de lintestingrle Mouvement gnral des

    cellules vers le sommet desvillosits

    Toutefois quelques cellules(dont certaines cellulescaliciformes et cellules

    entro-endocrines) sediffrencient quand ellessont encore dans lescryptes

    Les cellules de Paneth

    Situes au fond descryptes

    Dure de vie limite Remplaces par la

    descendance des cellules

    souches

    C di i l

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    Fig 22-19 B

    Coupe dintestin grleVillositsCryptes

    Cellules caliciformesen rouge

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    Les cellules souches

    Localisation dans la profondeurdes cryptes

    Donnent 4 types de cellulesdiffrencies1. Cellules absorbantes2. Cellules caliciformes3. Cellules de Paneth4. Cellules endocrines

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    2 - Cellules caliciformes

    Comme dans lpithliumrespiratoire

    Secrtent du mucus Migrent de la rgion des cellules

    souches vers la surface des

    villosits

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    Cryptdynes

    Precursor to corticostatin/defensin-related peptide

    accumulates to high levels in mouseintestinal crypt epithelium duringpostnatal development

    70-amino acid residues amino acid sequence given in first

    source

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    4 - Cellules endocrines

    Plus de 15 sous-types Scrtent srotonine et hormones

    peptidiques (comme la cholcystokinine)

    Action sur les neurones et autres typescellulaires de lintestin Rgulation de la croissance, prolifration

    activits des cellules du tube digestif et autrestissus

    Action sur le systme nerveux (comme desneuropeptides)

    Migrent de la rgion des cellules souches

    vers la surface des villosits

    Vi t d

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    Fig 22-20 A

    Viennent descellules souchesmultipotentes

    indiffrencies dufond des cryptesCellules

    absorbantesmicrovillosits Absorption Ancrage des

    enzymes dedigestion

    Cellulescaliciformes

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    Fig 22-20 B

    Cellules entro-endocrines Cellules de Paneth

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    Renouvellement des 4

    types de cellules Cellules absorbantes Cellules caliciformes

    Cellules endocrines Cellules de Paneth

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    Cellules absorbantes

    Cellules caliciformesCellules endocrines

    Migrent de la rgion des cellulessouches vers la surface des villosits

    tape damplification transitoire En sortant de la crypte les prcurseurs dj

    engags dans la diffrenciation subissent 4 6 divisions rapides puis arrtent leurdivisions et terminent leur diffrenciation

    2 5 jours entre les cryptes et la mort parapoptose au sommet des villosits

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    Mystre

    Origine des forces qui conduisent aumouvement de ces cellules

    Rle de la lame basale ?Sous-units de laminine 1 et 2 lame

    basale des cryptes

    Sous-units de laminine 5 gradientdans les villosits avec un maximum ausommet

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    Maintien de la population de

    cellules souches de lintestin1. Deux questions

    2. Voie Notch3. Voie Wnt

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    1 - Deux questions

    1. Quest ce qui contrle le choix dunecellule

    de garder ses caractres de cellules souche ou de sengager dans une voie de

    diffrenciation ?

    2. Quest ce qui conduit la diversificationde la cellule souche en 4 types decellules diffrencies ?

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    2 - Receptors, Notch

    A family of conserved cell surfacereceptors that contain EPIDERMALGROWTH FACTOR repeats in theirextracellular domain and ANKYRINrepeats in their cytoplasmic domains.

    The cytoplasmic domain of notchreceptors is released upon ligandbinding and translocates to the CELLNUCLEUS where it acts as transcriptionfactor.

    P th i

    t d f th d i

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    Sci. STKE, 5 December 2006

    Vol. 2006, Issue 364, p. cm7

    Notch Signaling Pathway.

    Matthias Ehebauer, Penelope

    Hayward, and Alfonso

    Martinez-Arias

    Pathway image captured from the dynamic

    graphical display of the information in the

    Connections Maps available 05 December 2006.

    For a key to the colors and symbols and to access

    the underlying data, please visit the pathway

    (http://stke.sciencemag.org/cgi/cm/stkecm;CMP_1

    9043).

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    3 - Wnt Proteins

    Wnt proteins are a large family of secretedglycoproteins that play essential roles inEMBRYONIC AND FETAL DEVELOPMENT, andtissue maintenance.

    They bind to FRIZZLED RECEPTORS and actas PARACRINE PROTEIN FACTORS to initiatea variety of SIGNAL TRANSDUCTIONPATHWAYS.

    The canonical Wnt signaling pathwaystabilizes the transcriptional coactivatorBETA CATENIN.

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    Frizzled Receptors

    A family of seven-pass transmembranecell-surface receptors.

    They contain an extracellular cysteine-rich domain and are receptors for WNTPROTEINS.

    Frizzled receptors often couple with

    HETEROTRIMERIC G PROTEINS andregulate multiple SIGNALTRANSDUCTION PATHWAYS.

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    http://www.stanford.edu/~rnusse/pathways/cell2.html

    usse p e

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    usse, p ebiology: relays at the

    membrane. Nature. 2005,438(7069):747-9.

    Crucial kinases. a, In cells not activated by Wnt, a complex between -catenin, Axin, APC andGSK3 causes phosphorylation of -catenin and its consequent destruction. The Wnt receptorsLRP6 and Frizzled are unoccupied. b, Without Axin, -catenin is stabilized and it enters thenucleus to control gene expression. Inset, binding of Wnt to cells results in phosphorylation (P) ofLRP6 residues in its cytoplasmic tail. Zeng et al.and Davidson et al.show that this is catalysed bythe GSK3 and CK1protein kinases. CK1is attached to the membrane by a lipid anchor domain.

    Several other sites on LRP6 that become phosphorylated are not shown here. The phosphorylatedLRP6 recruits Axin, removing it from the -catenin destruction complex and stabilizing -catenin.

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    Voie Wnt

    LEF-1/TCF : famille de protines rgulatricesde gnes impliques dans la voie Wnt Une souris dficientedans une de ces

    protines

    Pas de cryptes Pas de cellules souches absence de renouvellement de lpithlium form

    pendant la vie ftale

    Mort prcoce Hyperactivationde la voie Wnt chez ladulte

    (par mutation du gne APC par exemple) Hyperprolifration des cellules des cryptes

    Souvent cancer

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    Stefan Hoppler and Claire Louise

    Kavanagh.Wnt signalling: variety at thecoreJournal of Cell Science120, 385-393

    (2007)

    TCF/LEF (T-cell factor/lymphod enhancer factor) function in intestine and colorectal cancer. The stem cellpopulation at the base of the crypt in the intestine produces a proliferating progenitor cell population thatmigrates up the side of the crypt. Upon reaching the crypt-villus junction, cells begin to differentiate andcontinue moving up the villus until mature cells are shed into the lumen at the tip of the villus. The levelsof nuclear -catenin, and therefore active TCF/LEF, are highest at the base of the crypt in the stem celland proliferating progenitor population. In this population it is proposed that full-length TCF-4 (activating,green) and NTCF-1 (repressing, red) are the main active TCF/LEFs. However, when mutated Wntsignalling leads to colorectal cancer, ectopic expression of full-length LEF-1 is readily detected. As a resultthe predominant TCF/LEF isoforms present in colorectal cancer are activating (green) as opposed to

    repressive (red) TCF/LEFs. The levels of nuclear -catenin in colorectal cancer are very high because Wntsignalling pathway mutations mean that -catenin cannot be degraded.

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    Warren Strober

    Science25 August 2006 Vol 313,Issue 5790, Pages 1016-1145Unraveling Gut Inflammation

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