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Current Gastroenterology Reports
Erschienen in: Current Gastroenterology Reports 5/2010

01.10.2010

Intestinal Stem Cells

verfasst von: Shahid Umar

Erschienen in: Current Gastroenterology Reports | Ausgabe 5/2010

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Abstract

Self-renewal in the intestinal epithelia is fueled by a population of undifferentiated intestinal stem cells (ISCs) that give rise to daughter or progenitor cells, which can subsequently differentiate into the mature cell types required for normal gut function. The cellular signals that regulate self-renewal are poorly understood and the factors that mediate the transition from a stem cell to a progenitor cell in the gut are unknown. Recent studies have suggested that ISCs are located either at the crypt base interspersed between the Paneth cells (eg, Lgr-5+ve cells) or at or near position 4 within the intestinal crypt (eg, DCAMKL-1 or Bmi-1+ve cells). This raises the possibility that distinct stem cell regions exist in the crypts and that ISC’s state of activation will determine how the self-renewal is regulated in the intestinal tract.
Literatur
1.
Crosnier C, Stamataki D, Lewis J: Organizing cell renewal in the intestine: stem cells, signals and combinatorial control. Nat Rev Genet 2006, 7:349–359.CrossRefPubMed
2.
de Santa Barbara P, van den Brink GR, Roberts DJ: Development and differentiation of the intestinal epithelium. Cell Mol Life Sci 2003, 60:1322–1332.CrossRefPubMed
3.
Schmidt GH, Winton DJ, Ponder BA: Development of the pattern of cell renewal in the crypt-villus unit of chimeric mouse small intestine. Development 1988, 103:785–790.PubMed
4.
Cheng H, Leblond CP: Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. V. Unitarian Theory of the origin of the four epithelial cell types. Am J Anat 1974, 141:537–561.CrossRefPubMed
5.
Wright NA: Epithelial stem cell repertoire in the gut: clues to the origin of cell lineages, proliferative units and cancer. Int J Exp Pathol 2000, 81:117–143.CrossRefPubMed
6.
Potten CS, Loeffler M: Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development 1990, 110:1001–1020.PubMed
7.
Gordon JI, Schmidt GH, Roth KA: Studies of intestinal stem cells using normal, chimeric, and transgenic mice. FASEB J 1992, 6:3039–3050.PubMed
8.
Potten CS: Stem cells in gastrointestinal epithelium: numbers, characteristics and death. Philos Trans R Soc Lond B Biol Sci 1998, 353:821–830.CrossRefPubMed
9.
Bjerknes M, Cheng H: The stem-cell zone of the small intestinal epithelium. I. Evidence from Paneth cells in the adult mouse. Am J Anat 1981, 160:51–63.CrossRefPubMed
10.
Blanpain C, Horsley V, Fuchs E: Epithelial stem cells: turning over new leaves. Cell 2007,128:445–458.CrossRefPubMed
11.
12.
Korinek V, Barker N, Moerer P, et al.: Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nat Genet 1998, 19:379–383.CrossRefPubMed
13.
Kim BM, Mao J, Taketo MM, et al.: Phases of canonical Wnt signaling during the development of mouse intestinal epithelium. Gastroenterology 2007, 133:529–538.CrossRefPubMed
14.
van de Wetering M, Sancho E, Verweij C, et al.: The β-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 2002, 111:241–250.CrossRefPubMed
15.
Gregorieff A, Pinto D, Begthel H, et al.: Expression pattern of Wnt signaling components in the adult intestine. Gastroenterology 2005, 129:626–638.PubMed
16.
Byun T, Karimi M, Marsh JL, et al.: Expression of secreted Wnt antagonists in gastrointestinal tissues: potential role in stem cell homeostasis. J Clin Pathol 2005, 58:515–519.CrossRefPubMed
17.
Madison BB, Braunstein K, Kuizon E, et al.: Epithelial hedgehog signals pattern the intestinal crypt-villus axis. Development 2005, 132:279–289.CrossRefPubMed
18.
Bitgood MJ, McMahon AP: Hedgehog and Bmp genes are co-expressed at many diverse sites of cell-cell interaction in the mouse embryo. Dev Biol 1995, 172:126–138.CrossRefPubMed
19.
• Zacharias WJ, Li X, Madison BB, et al.: Hedgehog is an anti-inflammatory epithelial signal for the intestinal lamina propria. Gastroenterology 2010, 138:2368–2377. This article investigates the effects of chronic Hedgehog (Hh) inhibition in vivo by profiling molecular pathways acutely modulated by Hh signaling in the intestinal mesenchyme.CrossRefPubMed
20.
He XC, Zhang J, Tong WG, et al.: BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-β-catenin signaling. Nat Genet 2004, 36:1117–1121.CrossRefPubMed
21.
Haramis AP, Begthel H, van den Born M, et al.: De novo crypt formation and juvenile polyposis on BMP inhibition in mouse intestine. Science 2004, 303:1684–1686.CrossRefPubMed
22.
Louvi A, Artavanis-Tsakonas S: Notch signaling in vertebrate neural development. Nat Rev Neurosci 2006, 7:93–102.CrossRefPubMed
23.
24.
Fortini ME: Gamma-secretase-mediated proteolysis in cell-surface-receptor signaling. Nat Rev Mol Cell Biol 2002, 3:673–684.CrossRefPubMed
25.
Kao HY, Ordentlich P, Koyano-Nakagawa N, et al.: A histone deacetylase corepressor complex regulates the Notch signal transduction pathway. Genes Dev 1998, 12:2269–2277.CrossRefPubMed
26.
Lai EC: Keeping a good pathway down: transcriptional repression of Notch pathway target genes by CSL proteins. EMBO Rep 2002, 3:840–845.CrossRefPubMed
27.
Iso T, Kedes L, Hamamori Y: HES and HERP families: multiple effectors of the Notch signaling pathway. J Cell Physiol 2003, 194:237–255.CrossRefPubMed
28.
Fre S, Huyghe M, Mourikis P, et al.: Notch signals control the fate of immature progenitor cells in the intestine. Nature 2005, 435:964–968.CrossRefPubMed
29.
van der Flier LG, Clevers H: Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu Rev Physiol 2008, 71:241–260.CrossRef
30.
Potten CS: Extreme sensitivity of some intestinal crypt cells to X and gamma irradiation. Nature 1977, 269:518–521.CrossRefPubMed
31.
Potten CS, Owen G, Booth D: Intestinal stem cells protect their genome by selective segregation of template DNA strands. J Cell Sci 2002, 115:2381–2388.PubMed
32.
Winton DJ, Blount MA, Ponder BAJ: A clonal marker induced by mutation in mouse intestinal epithelium. Nature 1988, 333:463–466.CrossRefPubMed
33.
He XC, Yin T, Grindley JC, et al.: PTEN-deficient intestinal stem cells initiate intestinal polyposis. Nat Genet 2007, 39:189–198.CrossRefPubMed
34.
Barker N, van de Wetering M, Clevers H: The intestinal stem cell. Genes Dev 2008, 22:1856–1864.CrossRefPubMed
35.
Scoville DH, Sato T, He XC, et al.: Current view: intestinal stem cells and signaling. Gastroenterology 2008, 134:849–864.CrossRefPubMed
36.
Bjerknes M, Cheng H: Clonal analysis of mouse intestinal epithelial progenitors. Gastroenterology 1999, 116:7–14.CrossRefPubMed
37.
Batlle E, Henderson JT, Beghtel H, et al.: Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. Cell 2002, 111:251–263.CrossRefPubMed
38.
Wielenga VJ, Smits R, Korinek V, et al.: Expression of CD44 in Apc and Tcf mutant mice implies regulation by the WNT pathway. Am J Pathol 1999, 154:515–523.PubMed
39.
Kayahara T, Sawada M, Takaishi S, et al.: Candidate markers for stem and early progenitor cells, Musashi-1 and Hes1, are expressed in crypt base columnar cells of mouse small intestine. FEBS Lett 2003, 535:131–135.CrossRefPubMed
40.
Potten CS, Booth C, Tudor GL, et al.: Identification of a putative intestinal stem cell and early lineage marker musashi-1. Differentiation 2003, 71:28–41.CrossRefPubMed
41.
Tian Q, Feetham MC, Tao WA, et al.: Proteomic analysis identifies that 14-3-3zeta interacts with beta-catenin and facilitates its activation by Akt. Proc Natl Acad Sci U S A 2004, 101:15370–15375.CrossRefPubMed
42.
Dekaney CM, Rodriguez JM, Graul MC, et al.: Isolation and characterization of a putative intestinal stem cell fraction from mouse jejunum. Gastroenterology 2005, 129:1567–1580.CrossRefPubMed
43.
Gulati AS, Ochsner SA, Henning SJ: Molecular properties on side population-sorted cells from mouse small intestine. Am J Physiol Gastrointest Liver Physiol 2008, 294:G286–G294.CrossRefPubMed
44.
Vidrich A, Buzan JM, Ilo C, et al.: Fibroblast growth factor receptor-3 is expressed in undifferentiated intestinal epithelial cells during murine crypt morphogenesis. Dev Dyn 2004, 230:114–123.CrossRefPubMed
45.
Blache P, van de Wetering M, Duluc I, et al.: SOX9 is an intestine crypt transcription factor, is regulated by the Wnt pathway, and represses the CDX2 and MUC2 genes. J Cell Biol 2004, 166:37–47.CrossRefPubMed
46.
Van der Flier LG, Sabates-Bellver J, Oving I, et al.: The intestinal Wnt/TCF signature. Gastroenterology 2007, 132:628–632.CrossRefPubMed
47.
Breault DT, Min IM, Carlone DL, et al.: Generation of mTert-GFP mice as a model to identify and study tissue progenitor cells. Proc Natl Acad Sci U S A 2008, 105:10420–10425.CrossRefPubMed
48.
Stappenbeck TS, Mills JC, Gordon JI: Molecular features of adult mouse small intestinal epithelial progenitors. Proc Natl Acad Sci U S A 2003, 100:1004–1009.CrossRefPubMed
49.
Giannakis M, Stappenbeck TS, Mills JC, et al.: Molecular properties of adult mouse gastric and intestinal epithelial progenitors in their niches. J Biol Chem 2006, 281:11292–11300.CrossRefPubMed
50.
Potten CS, Booth C, Pritchard DM: The intestinal epithelial stem cell: the mucosal governor. Int J Exp Pathol 1997, 78:219–243.CrossRefPubMed
51.
•• Barker N, van Es JH, Kuipers J, et al.: Identification of stem cells in small intestine and colon by marker gene LGR5. Nature 2007, 449:1003–1008. Using knock-in alleles, this elegant study identifies stem cells in small intestine and colon by marker gene Lgr5.CrossRefPubMed
52.
Potten CS, Gandara R, Mahida YR, et al.: The stem cells of small intestinal crypts: where are they? Cell Prolif 2009, 42:731–750.CrossRefPubMed
53.
Zhu L, Gibson P, Currle DS, Tong Y, et al.: Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature 2009, 457:603–607.CrossRefPubMed
54.
van der Flier LG, Haegebarth A, Stange DE, et al.: OLFM4 is a robust marker for stem cells in human intestine and marks a subset of colorectal cancer cells. Gastroenterology 2009, 137:15–17.CrossRefPubMed
55.
•• Sangiorgi E, Capecchi MR: Bmi1 is expressed in vivo in intestinal stem cells. Nat Genet 2008, 40:915–920. Using a mouse expressing a tamoxifen-inducible Cre from the Bmi1 locus, this study identifies Bmi1 as an ISC marker in vivo.CrossRefPubMed
56.
•• May R, Riehl TE, Hunt C, et al.: Identification of a novel putative gastrointestinal stem cell and adenoma stem cell marker, doublecortin and CaM kinase-like-1, following radiation injury and in adenomatous polyposis coli/multiple intestinal neoplasia mice. Stem Cells 2008, 26:630–637. Using the radiation injury and APC/Min mouse models, this study identifies DCAMKL-1 as an ISC marker in vivo.CrossRefPubMed
57.
Giannakis M, Chen SL, Karam SM, et al.: Helicobacter pylori evolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells. Proc Natl Acad Sci U S A 2008, 105:4358–4363.CrossRefPubMed
58.
• May R, Sureban SM, Hoang N, et al.: Doublecortin and CaM kinase-like-1 and leucine-rich-repeat-containing G-protein-coupled receptor mark quiescent and cycling intestinal stem cells, respectively. Stem Cells 2009, 27:2571–2579. Using the modified label-retention assay, this study compares the quiescent versus actively cycling nature of the intestinal stem markers DCAMKL-1 and Lgr5, respectively.CrossRefPubMed
59.
Potten CS: A comprehensive study of the radiobiological response of the murine (BDF1) small intestine. Int J Rad Biol 1990, 58:925–973.CrossRefPubMed
60.
Pizarro TT, Arseneau KO, Cominelli F: Lessons from genetically engineered animal models XI. Novel mouse models to study pathogenic mechanisms of Crohn’s disease. Am J Physiol 2000, 278:G665–G669.
61.
Jobin C, Sartor RB: The I kappa B/NF-kappa B system: a key determinant of mucosal inflammation and protection. Am J Physiol 2000, 278:C451–C462.
62.
Karin M: Nuclear factor-κB in cancer development and progression. Nature 2006, 441:431–436.CrossRefPubMed
63.
Wehkamp J, Wang G, Kubler I, et al.: The Paneth cell alpha defensin deficiency of ileal Crohn’s disease is linked to Wnt/Tcf-4. J Immunol 2007, 179:3109–3118.PubMed
64.
Riehl T, Cohn S, Tessner T, et al.: Lipopolysaccharide is radioprotective in the mouse intestine through a prostaglandin-mediated mechanism. Gastroenterology 2000, 118:1106–1116.CrossRefPubMed
65.
Houchen CW, George RJ, Sturmoski MA, et al.: FGF-2 enhances intestinal stem cell survival and its expression is induced after radiation injury. Am J Physiol 1999, 276:G249–G258.PubMed
66.
Wu S, Miyamoto T: Radioprotection of the intestinal crypts of mice by recombinant human interlukin-1. Radiat Res 1990, 123:112–115.CrossRefPubMed
67.
Somosy Z, Horvath G, Telbisz A, et al.: Morphological aspects of ionizing radiation response of small intestine. Micron 2002, 33:167–178.CrossRefPubMed
Metadaten
Titel
Intestinal Stem Cells
verfasst von
Shahid Umar
Publikationsdatum
01.10.2010
Verlag
Current Science Inc.
Erschienen in
Current Gastroenterology Reports / Ausgabe 5/2010
Print ISSN: 1522-8037
Elektronische ISSN: 1534-312X
DOI
https://doi.org/10.1007/s11894-010-0130-3

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