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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