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Annual Review of Physiology

Volume 82, 2020

Intestinal Stem Cell Aging: Origins and Interventions

Abstract

Regenerative processes that maintain the function of the gastrointestinal (GI) epithelium are critical for health and survival of multicellular organisms. In insects and vertebrates, intestinal stem cells (ISCs) regenerate the GI epithelium. ISC function is regulated by intrinsic, local, and systemic stimuli to adjust regeneration to tissue demands. These control mechanisms decline with age, resulting in significant perturbation of intestinal homeostasis. Processes that lead to this decline have been explored intensively in in recent years and are now starting to be characterized in mammalian models. This review presents a model for age-related regenerative decline in the fly intestine and discusses recent findings that start to establish molecular mechanisms of age-related decline of mammalian ISC function.

Keyword(s): aging, barrier epithelium, Drosophila, intestinal stem cells, regeneration
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/content/journals/10.1146/annurev-physiol-021119-034359
2020-02-10
2024-04-19
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Literature Cited

  1. 1. 
    Simons BD, Clevers H. 2011. Stem cell self-renewal in intestinal crypt. Exp. Cell Res. 317:2719–24
     [Google Scholar]
  2. 2. 
    Rock JR, Hogan BL. 2011. Epithelial progenitor cells in lung development, maintenance, repair, and disease. Annu. Rev. Cell Dev. Biol. 27:493–512
     [Google Scholar]
  3. 3. 
    Rando TA. 2006. Stem cells, ageing and the quest for immortality. Nature 441:1080–86
     [Google Scholar]
  4. 4. 
    Biteau B, Hochmuth CE, Jasper H 2011. Maintaining tissue homeostasis: dynamic control of somatic stem cell activity. Cell Stem Cell 9:402–11
     [Google Scholar]
  5. 5. 
    Neves J, Sousa-Victor P, Jasper H 2017. Rejuvenating strategies for stem cell-based therapies in aging. Cell Stem Cell 20:161–75
     [Google Scholar]
  6. 6. 
    Jones DL, Rando TA. 2011. Emerging models and paradigms for stem cell ageing. Nat. Cell Biol. 13:506–12
     [Google Scholar]
  7. 7. 
    Chandel NS, Jasper H, Ho TT, Passegue E 2016. Metabolic regulation of stem cell function in tissue homeostasis and organismal ageing. Nat. Cell Biol. 18:823–32
     [Google Scholar]
  8. 8. 
    Li H, Jasper H. 2016. Gastrointestinal stem cells in health and disease: from flies to humans. Dis. Model. Mech. 9:487–99
     [Google Scholar]
  9. 9. 
    Wang L, Karpac J, Jasper H 2014. Promoting longevity by maintaining metabolic and proliferative homeostasis. J. Exp. Biol. 217:109–18
     [Google Scholar]
  10. 10. 
    Jasper H, Kennedy BK. 2012. Niche science: the aging stem cell. Cell Cycle 11:2959–60
     [Google Scholar]
  11. 11. 
    Ayyaz A, Jasper H. 2013. Intestinal inflammation and stem cell homeostasis in aging Drosophila melanogaster. Front. Cell. Infect. Microbiol 3:98
     [Google Scholar]
  12. 12. 
    Miguel-Aliaga I, Jasper H, Lemaitre B 2018. Anatomy and physiology of the digestive tract of Drosophila melanogaster. Genetics 210:357–96
     [Google Scholar]
  13. 13. 
    Tata PR, Mou H, Pardo-Saganta A, Zhao R, Prabhu M et al. 2013. Dedifferentiation of committed epithelial cells into stem cells in vivo. Nature 503:218–23
     [Google Scholar]
  14. 14. 
    Lucchetta EM, Ohlstein B. 2017. Amitosis of polyploid cells regenerates functional stem cells in the Drosophila intestine. Cell Stem Cell 20:609–20.e6
     [Google Scholar]
  15. 15. 
    Tian H, Biehs B, Warming S, Leong KG, Rangell L et al. 2011. A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature 478:255–59
     [Google Scholar]
  16. 16. 
    Tetteh PW, Basak O, Farin HF, Wiebrands K, Kretzschmar K et al. 2016. Replacement of lost Lgr5-positive stem cells through plasticity of their enterocyte-lineage daughters. Cell Stem Cell 18:203–13
     [Google Scholar]
  17. 17. 
    Barker N, Bartfeld S, Clevers H 2010. Tissue-resident adult stem cell populations of rapidly self-renewing organs. Cell Stem Cell 7:656–70
     [Google Scholar]
  18. 18. 
    Buchon N, Osman D, David FP, Fang HY, Boquete JP et al. 2013. Morphological and molecular characterization of adult midgut compartmentalization in Drosophila. Cell Rep 3:1725–38
     [Google Scholar]
  19. 19. 
    Marianes A, Spradling AC. 2013. Physiological and stem cell compartmentalization within the Drosophila midgut. eLife 2:e00886
     [Google Scholar]
  20. 20. 
    Li H, Qi Y, Jasper H 2013. Dpp signaling determines regional stem cell identity in the regenerating adult Drosophila gastrointestinal tract. Cell Rep 4:10–18
     [Google Scholar]
  21. 21. 
    Strand M, Micchelli CA. 2011. Quiescent gastric stem cells maintain the adult Drosophila stomach. PNAS 108:17696–701
     [Google Scholar]
  22. 22. 
    Clemente JC, Ursell LK, Parfrey LW, Knight R 2012. The impact of the gut microbiota on human health: an integrative view. Cell 148:1258–70
     [Google Scholar]
  23. 23. 
    Gonda TA, Tu S, Wang TC 2009. Chronic inflammation, the tumor microenvironment and carcinogenesis. Cell Cycle 8:2005–13
     [Google Scholar]
  24. 24. 
    Kaser A, Zeissig S, Blumberg RS 2010. Inflammatory bowel disease. Annu. Rev. Immunol. 28:573–621
     [Google Scholar]
  25. 25. 
    Kostic AD, Gevers D, Pedamallu CS, Michaud M, Duke F et al. 2012. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res 22:292–98
     [Google Scholar]
  26. 26. 
    Niwa T, Tsukamoto T, Toyoda T, Mori A, Tanaka H et al. 2010. Inflammatory processes triggered by Helicobacter pylori infection cause aberrant DNA methylation in gastric epithelial cells. Cancer Res 70:1430–40
     [Google Scholar]
  27. 27. 
    Uronis JM, Mühlbauer M, Herfarth HH, Rubinas TC, Jones GS, Jobin C 2009. Modulation of the intestinal microbiota alters colitis-associated colorectal cancer susceptibility. PLOS ONE 4:e6026
     [Google Scholar]
  28. 28. 
    Patel BB, Yu Y, Du J, Levi E, Phillip PA, Majumdar APN 2009. Age-related increase in colorectal cancer stem cells in macroscopically normal mucosa of patients with adenomas: a risk factor for colon cancer. Biochem. Biophys. Res. Commun. 378:344–47
     [Google Scholar]
  29. 29. 
    Roberts SB, Rosenberg I. 2006. Nutrition and aging: changes in the regulation of energy metabolism with aging. Physiol. Rev. 86:651–67
     [Google Scholar]
  30. 30. 
    Duncan SH, Flint HJ. 2013. Probiotics and prebiotics and health in ageing populations. Maturitas 75:44–50
     [Google Scholar]
  31. 31. 
    Kallus SJ, Brandt LJ. 2012. The intestinal microbiota and obesity. J. Clin. Gastroenterol. 46:16–24
     [Google Scholar]
  32. 32. 
    De Bandt J-P, Waligora-Dupriet A-J, Butel M-J 2011. Intestinal microbiota in inflammation and insulin resistance: relevance to humans. Curr. Opin. Clin. Nutr. Metab. Care 14:334–40
     [Google Scholar]
  33. 33. 
    Claesson MJ, Jeffery IB, Conde S, Power SE, O'Connor EM et al. 2012. Gut microbiota composition correlates with diet and health in the elderly. Nature 488:178–84
     [Google Scholar]
  34. 34. 
    Slack JM. 2007. Metaplasia and transdifferentiation: from pure biology to the clinic. Nat. Rev. Mol. Cell Biol. 8:369–78
     [Google Scholar]
  35. 35. 
    Falk GW. 2002. Barrett's esophagus. Gastroenterology 122:1569–91
     [Google Scholar]
  36. 36. 
    Hvid-Jensen F, Pedersen L, Drewes AM, Sorensen HT, Funch-Jensen P 2011. Incidence of adenocarcinoma among patients with Barrett's esophagus. N. Engl. J. Med. 365:1375–83
     [Google Scholar]
  37. 37. 
    Correa P, Houghton J. 2007. Carcinogenesis of Helicobacter pylori. Gastroenterology 133:659–72
     [Google Scholar]
  38. 38. 
    Ullman T, Odze R, Farraye FA 2009. Diagnosis and management of dysplasia in patients with ulcerative colitis and Crohn's disease of the colon. Inflamm. Bowel. Dis. 15:630–38
     [Google Scholar]
  39. 39. 
    Micchelli CA, Perrimon N. 2006. Evidence that stem cells reside in the adult Drosophila midgut epithelium. Nature 439:475–79
     [Google Scholar]
  40. 40. 
    Ohlstein B, Spradling A. 2006. The adult Drosophila posterior midgut is maintained by pluripotent stem cells. Nature 439:470–74
     [Google Scholar]
  41. 41. 
    Barker N, van Es JH, Kuipers J, Kujala P, van den Born M et al. 2007. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449:1003–7
     [Google Scholar]
  42. 42. 
    Haller S, Kapuria S, Riley RR, O'Leary MN, Schreiber KH et al. 2017. mTORC1 activation during repeated regeneration impairs somatic stem cell maintenance. Cell Stem Cell 21:806–18.e5
     [Google Scholar]
  43. 43. 
    Biteau B, Jasper H. 2014. Slit/Robo signaling regulates cell fate decisions in the intestinal stem cell lineage of Drosophila. Cell Rep 7:1867–75
     [Google Scholar]
  44. 44. 
    O'Brien LE, Soliman SS, Li X, Bilder D 2011. Altered modes of stem cell division drive adaptive intestinal growth. Cell 147:603–14
     [Google Scholar]
  45. 45. 
    Biteau B, Jasper H. 2011. EGF signaling regulates the proliferation of intestinal stem cells in. Development 138:1045–55
     [Google Scholar]
  46. 46. 
    Deng H, Gerencser AA, Jasper H 2015. Signal integration by Ca regulates intestinal stem-cell activity. Nature 528:212–17
     [Google Scholar]
  47. 47. 
    Xu C, Luo J, He L, Montell C, Perrimon N 2017. Oxidative stress induces stem cell proliferation via TRPA1/RyR-mediated Ca2+ signaling in the Drosophila midgut. eLife 6:e22441
     [Google Scholar]
  48. 48. 
    Singh SR, Zeng X, Zhao J, Liu Y, Hou G et al. 2016. The lipolysis pathway sustains normal and transformed stem cells in adult Drosophila. Nature 538:109–13
     [Google Scholar]
  49. 49. 
    Koehler CL, Perkins GA, Ellisman MH, Jones DL 2017. Pink1 and Parkin regulate Drosophila intestinal stem cell proliferation during stress and aging. J. Cell Biol. 216:2315–27
     [Google Scholar]
  50. 50. 
    Schell JC, Wisidagama DR, Bensard C, Zhao H, Wei P et al. 2017. Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism. Nat. Cell Biol. 19:1027–36
     [Google Scholar]
  51. 51. 
    Ferrandon D. 2013. The complementary facets of epithelial host defenses in the genetic model organism Drosophila melanogaster: from resistance to resilience. Curr. Opin. Immunol. 25:59–70
     [Google Scholar]
  52. 52. 
    Hegedus D, Erlandson M, Gillott C, Toprak U 2009. New insights into peritrophic matrix synthesis, architecture, and function. Annu. Rev. Entomol. 54:285–302
     [Google Scholar]
  53. 53. 
    Kuraishi T, Binggeli O, Opota O, Buchon N, Lemaitre B 2011. Genetic evidence for a protective role of the peritrophic matrix against intestinal bacterial infection in Drosophila melanogaster. PNAS 108:15966–71
     [Google Scholar]
  54. 54. 
    Nehme NT, Liégeois S, Kele B, Giammarinaro P, Pradel E et al. 2007. A model of bacterial intestinal infections in Drosophila melanogaster. PLOS Pathog 3:e173
     [Google Scholar]
  55. 55. 
    Liehl P, Blight M, Vodovar N, Boccard F, Lemaitre B 2006. Prevalence of local immune response against oral infection in a Drosophila/Pseudomonas infection model. PLOS Pathog 2:e56
     [Google Scholar]
  56. 56. 
    Ryu JH, Ha EM, Oh CT, Seol JH, Brey PT et al. 2006. An essential complementary role of NF-κB pathway to microbicidal oxidants in Drosophila gut immunity. EMBO J 25:3693–701
     [Google Scholar]
  57. 57. 
    Tzou P, Ohresser S, Ferrandon D, Capovilla M, Reichhart JM et al. 2000. Tissue-specific inducible expression of antimicrobial peptide genes in Drosophila surface epithelia. Immunity 13:737–48
     [Google Scholar]
  58. 58. 
    Buchon N, Broderick NA, Chakrabarti S, Lee W-J, Lemaitre B 2009. Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila. Genes Dev 23:2333–44
     [Google Scholar]
  59. 59. 
    Zaidman-Rémy A, Hervé M, Poidevin M, Pili-Floury S, Kim MS et al. 2006. The Drosophila amidase PGRP-LB modulates the immune response to bacterial infection. Immunity 24:463–73
     [Google Scholar]
  60. 60. 
    Bosco-Drayon V, Poidevin M, Boneca IG, Narbonne-Reveau K, Royet J, Charroux B 2012. Peptidoglycan sensing by the receptor PGRP-LE in the Drosophila gut induces immune responses to infectious bacteria and tolerance to microbiota. Cell Host Microbe 12:153–65
     [Google Scholar]
  61. 61. 
    Neyen C, Poidevin M, Roussel A, Lemaitre B 2012. Tissue- and ligand-specific sensing of gram-negative infection in Drosophila by PGRP-LC isoforms and PGRP-LE. J. Immunol. 189:1886–97
     [Google Scholar]
  62. 62. 
    Ferrandon D, Imler J-L, Hetru C, Hoffmann JA 2007. The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections. Nat. Rev. Immunol. 7:862–74
     [Google Scholar]
  63. 63. 
    Lemaitre B, Hoffmann J. 2007. The host defense of Drosophila melanogaster. Annu. Rev. Immunol 25:697–743
     [Google Scholar]
  64. 64. 
    Ha EM, Lee KA, Seo YY, Kim SH, Lim JH et al. 2009. Coordination of multiple dual oxidase-regulatory pathways in responses to commensal and infectious microbes in Drosophila gut. Nat. Immunol. 10:949–57
     [Google Scholar]
  65. 65. 
    Buchon N, Broderick NA, Lemaitre B 2013. Gut homeostasis in a microbial world: insights from Drosophila melanogaster. Nat. Rev. Microbiol 11:615–26
     [Google Scholar]
  66. 66. 
    Lee K-A, Kim S-H, Kim E-K, Ha E-M, You H et al. 2013. Bacterial-derived uracil as a modulator of mucosal immunity and gut-microbe homeostasis in Drosophila. Cell 153:797–811
     [Google Scholar]
  67. 67. 
    Davis MM, Engström Y. 2012. Immune response in the barrier epithelia: lessons from the fruit fly Drosophila melanogaster. J. Innate Immun 4:273–83
     [Google Scholar]
  68. 68. 
    Ryu JH, Kim SH, Lee HY, Bai JY, Nam YD et al. 2008. Innate immune homeostasis by the homeobox gene Caudal and commensal-gut mutualism in Drosophila. Science 319:777–82
     [Google Scholar]
  69. 69. 
    Maillet F, Bischoff V, Vignal C, Hoffmann J, Royet J 2008. The Drosophila peptidoglycan recognition protein PGRP-LF blocks PGRP-LC and IMD/JNK pathway activation. Cell Host Microbe 3:293–303
     [Google Scholar]
  70. 70. 
    Paredes JC, Welchman DP, Poidevin M, Lemaitre B 2011. Negative regulation by amidase PGRPs shapes the Drosophila antibacterial response and protects the fly from innocuous infection. Immunity 35:770–79
     [Google Scholar]
  71. 71. 
    Thevenon D, Engel E, Avet-Rochex A, Gottar M, Bergeret E et al. 2009. The Drosophila ubiquitin-specific protease dUSP36/Scny targets IMD to prevent constitutive immune signaling. Cell Host Microbe 6:309–20
     [Google Scholar]
  72. 72. 
    Lhocine N, Ribeiro PS, Buchon N, Wepf A, Wilson R et al. 2008. PIMS modulates immune tolerance by negatively regulating Drosophila innate immune signaling. Cell Host Microbe 4:147–58
     [Google Scholar]
  73. 73. 
    Buchon N, Broderick NA, Poidevin M, Pradervand S, Lemaitre B 2009. Drosophila intestinal response to bacterial infection: activation of host defense and stem cell proliferation. Cell Host Microbe 5:200–11
     [Google Scholar]
  74. 74. 
    Biteau B, Karpac J, Supoyo S, Degennaro M, Lehmann R, Jasper H 2010. Lifespan extension by preserving proliferative homeostasis in Drosophila. PLOS Genet 6:e1001159
     [Google Scholar]
  75. 75. 
    Ha EM, Lee KA, Park SH, Kim SH, Nam HJ et al. 2009. Regulation of DUOX by the Gαq-phospholipase Cβ-Ca2+ pathway in Drosophila gut immunity. Dev. Cell 16:386–97
     [Google Scholar]
  76. 76. 
    Ryu JH, Ha EM, Lee WJ 2009. Innate immunity and gut-microbe mutualism in Drosophila. Dev. Comp. Immunol 34:369–76
     [Google Scholar]
  77. 77. 
    Ha EM, Oh CT, Bae YS, Lee WJ 2005. A direct role for dual oxidase in Drosophila gut immunity. Science 310:847–50
     [Google Scholar]
  78. 78. 
    Jiang H, Edgar BA. 2009. EGFR signaling regulates the proliferation of Drosophila adult midgut progenitors. Development 136:483–93
     [Google Scholar]
  79. 79. 
    Jiang H, Patel PH, Kohlmaier A, Grenley MO, McEwen DG, Edgar BA 2009. Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell 137:1343–55
     [Google Scholar]
  80. 80. 
    Biteau B, Hochmuth CE, Jasper H 2008. JNK activity in somatic stem cells causes loss of tissue homeostasis in the aging Drosophila gut. Cell Stem Cell 3:442–55
     [Google Scholar]
  81. 81. 
    Shin SC, Kim SH, You H, Kim B, Kim AC et al. 2011. Drosophila microbiome modulates host developmental and metabolic homeostasis via insulin signaling. Science 334:670–74
     [Google Scholar]
  82. 82. 
    Storelli G, Defaye A, Erkosar B, Hols P, Royet J, Leulier F 2011. Lactobacillus plantarum promotes drosophila systemic growth by modulating hormonal signals through TOR-dependent nutrient sensing. Cell Metab 14:403–14
     [Google Scholar]
  83. 83. 
    Wong CN, Ng P, Douglas AE 2011. Low-diversity bacterial community in the gut of the fruitfly Drosophila melanogaster. Environ. Microbiol 13:1889–900
     [Google Scholar]
  84. 84. 
    Chandler JA, Lang JM, Bhatnagar S, Eisen JA, Kopp A 2011. Bacterial communities of diverse Drosophila species: ecological context of a host-microbe model system. PLOS Genet 7:e1002272
     [Google Scholar]
  85. 85. 
    Li H, Qi Y, Jasper H 2016. Preventing age-related decline of gut compartmentalization limits microbiota dysbiosis and extends lifespan. Cell Host Microbe 19:240–53
     [Google Scholar]
  86. 86. 
    Iatsenko I, Boquete JP, Lemaitre B 2018. Microbiota-derived lactate activates production of reactive oxygen species by the intestinal NADPH oxidase Nox and shortens Drosophila lifespan. Immunity 49:929–42.e5
     [Google Scholar]
  87. 87. 
    Fast D, Duggal A, Foley E 2018. Monoassociation with Lactobacillus plantarum disrupts intestinal homeostasis in adult Drosophila melanogaster. mBio 9:e01114–18
     [Google Scholar]
  88. 88. 
    Choi NH, Kim JG, Yang DJ, Kim YS, Yoo MA 2008. Age-related changes in Drosophila midgut are associated with PVF2, a PDGF/VEGF-like growth factor. Aging Cell 7:318–34
     [Google Scholar]
  89. 89. 
    Hochmuth CE, Biteau B, Bohmann D, Jasper H 2011. Redox regulation by Keap1 and Nrf2 controls intestinal stem cell proliferation in Drosophila. Cell Stem Cell 8:188–99
     [Google Scholar]
  90. 90. 
    Rera M, Bahadorani S, Cho J, Koehler CL, Ulgherait M et al. 2011. Modulation of longevity and tissue homeostasis by the Drosophila PGC-1 homolog. Cell Metab 14:623–34
     [Google Scholar]
  91. 91. 
    Guo L, Karpac J, Tran SL, Jasper H 2014. PGRP-SC2 promotes gut immune homeostasis to limit commensal dysbiosis and extend lifespan. Cell 156:109–22
     [Google Scholar]
  92. 92. 
    Chen H, Zheng X, Zheng Y 2014. Age-associated loss of lamin-B leads to systemic inflammation and gut hyperplasia. Cell 159:829–43
     [Google Scholar]
  93. 93. 
    Wang L, Ryoo HD, Qi Y, Jasper H 2015. PERK limits Drosophila lifespan by promoting intestinal stem cell proliferation in response to ER stress. PLOS Genet 11:e1005220
     [Google Scholar]
  94. 94. 
    Siudeja K, Nassari S, Gervais L, Skorski P, Lameiras S et al. 2015. Frequent somatic mutation in adult intestinal stem cells drives neoplasia and genetic mosaicism during aging. Cell Stem Cell 17:663–74
     [Google Scholar]
  95. 95. 
    Clark RI, Salazar A, Yamada R, Fitz-Gibbon S, Morselli M et al. 2015. Distinct shifts in microbiota composition during Drosophila aging impair intestinal function and drive mortality. Cell Rep 12:1656–67
     [Google Scholar]
  96. 96. 
    Rera M, Clark R, Walker D 2012. Intestinal barrier dysfunction links metabolic and inflammatory markers of aging to death in Drosophila. PNAS 109:21528–33
     [Google Scholar]
  97. 97. 
    Akagi K, Wilson KA, Katewa SD, Ortega M, Simons J et al. 2018. Dietary restriction improves intestinal cellular fitness to enhance gut barrier function and lifespan in D. melanogaster. PLOS Genet 14:e1007777
     [Google Scholar]
  98. 98. 
    Regan JC, Khericha M, Dobson AJ, Bolukbasi E, Rattanavirotkul N, Partridge L 2016. Sex difference in pathology of the ageing gut mediates the greater response of female lifespan to dietary restriction. eLife 5:e10956
     [Google Scholar]
  99. 99. 
    Salazar AM, Resnik-Docampo M, Ulgherait M, Clark RI, Shirasu-Hiza M et al. 2018. Intestinal snakeskin limits microbial dysbiosis during aging and promotes longevity. Science 9:229–43
     [Google Scholar]
  100. 100. 
    Resnik-Docampo M, Sauer V, Schinaman JM, Clark RI, Walker DW, Jones DL 2018. Keeping it tight: the relationship between bacterial dysbiosis, septate junctions, and the intestinal barrier in Drosophila. Fly 12:34–40
     [Google Scholar]
  101. 101. 
    Resnik-Docampo M, Koehler CL, Clark RI, Schinaman JM, Sauer V et al. 2017. Tricellular junctions regulate intestinal stem cell behaviour to maintain homeostasis. Nat. Cell Biol. 19:52–59
     [Google Scholar]
  102. 102. 
    Rodriguez-Fernandez IA, Qi Y, Jasper H 2019. Loss of a proteostatic checkpoint in intestinal stem cells contributes to age-related epithelial dysfunction. Nat. Commun. 10:1050
     [Google Scholar]
  103. 103. 
    Sousa-Victor P, Ayyaz A, Hayashi R, Qi Y, Madden DT et al. 2017. Piwi is required to limit exhaustion of aging somatic stem cells. Cell Rep 20:2527–37
     [Google Scholar]
  104. 104. 
    Nagy P, Sandor GO, Juhasz G 2018. Autophagy maintains stem cells and intestinal homeostasis in Drosophila. Sci. Rep 8:4644
     [Google Scholar]
  105. 105. 
    Jeon HJ, Kim YS, Kim JG, Heo K, Pyo JH et al. 2018. Effect of heterochromatin stability on intestinal stem cell aging in Drosophila. Mech. Ageing Dev 173:50–60
     [Google Scholar]
  106. 106. 
    Filer D, Thompson MA, Takhaveev V, Dobson AJ, Kotronaki I et al. 2017. RNA polymerase III limits longevity downstream of TORC1. Nature 552:263–67
     [Google Scholar]
  107. 107. 
    Barker N. 2014. Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration. Nat. Rev. Mol. Cell Biol. 15:19–33
     [Google Scholar]
  108. 108. 
    Clevers H. 2013. The intestinal crypt, a prototype stem cell compartment. Cell 154:274–84
     [Google Scholar]
  109. 109. 
    Hermiston ML, Gordon JI. 1995. Organization of the crypt-villus axis and evolution of its stem cell hierarchy during intestinal development. Am. J. Physiol. Gastrointest. Liver Physiol. 268:G813–22
     [Google Scholar]
  110. 110. 
    Bjerknes M, Cheng H. 1999. Clonal analysis of mouse intestinal epithelial progenitors. Gastroenterology 116:7–14
     [Google Scholar]
  111. 111. 
    Ponder BA, Schmidt GH, Wilkinson MM, Wood MJ, Monk M, Reid A 1985. Derivation of mouse intestinal crypts from single progenitor cells. Nature 313:689–91
     [Google Scholar]
  112. 112. 
    Sangiorgi E, Capecchi MR. 2008. Bmi1 is expressed in vivo in intestinal stem cells. Nat. Genet. 40:915–20
     [Google Scholar]
  113. 113. 
    Yan KS, Chia LA, Li X, Ootani A, Su J et al. 2012. The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations. PNAS 109:466–71
     [Google Scholar]
  114. 114. 
    Li N, Yousefi M, Nakauka-Ddamba A, Jain R, Tobias J et al. 2014. Single-cell analysis of proxy reporter allele-marked epithelial cells establishes intestinal stem cell hierarchy. Stem Cell Rep 3:876–91
     [Google Scholar]
  115. 115. 
    Jones JC, Brindley CD, Elder NH, Myers MG Jr., Rajala MW, et al. Cellular plasticity of Defa4Cre-expressing Paneth cells in response to Notch activation and intestinal injury. Cell. Mol. Gastroenterol. Hepatol. 7:533–54
     [Google Scholar]
  116. 116. 
    Yu S, Tong K, Zhao Y, Balasubramanian I, Yap GS et al. 2018. Paneth cell multipotency induced by Notch activation following injury. Cell Stem Cell 23:46–59.e5
     [Google Scholar]
  117. 117. 
    Sei Y, Feng J, Samsel L, White A, Zhao X et al. Mature enteroendocrine cells contribute to basal and pathological stem cell dynamics in the small intestine. Am. J. Physiol. Gastrointest. Liver Physiol. 315:G495–510
     [Google Scholar]
  118. 118. 
    Ayyaz A, Kumar S, Sangiorgi B, Ghoshal B, Gosio J et al. 2019. Single-cell transcriptomes of the regenerating intestine reveal a revival stem cell. Nature 569:121–25
     [Google Scholar]
  119. 119. 
    Jung P, Sato T, Merlos-Suarez A, Barriga FM, Iglesias M et al. Isolation and in vitro expansion of human colonic stem cells. Nat. Med. 17:1225–27
     [Google Scholar]
  120. 120. 
    Forster R, Chiba K, Schaeffer L, Regalado SG, Lai CS et al. 2014. Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells. Stem Cell Rep 2:838–52
     [Google Scholar]
  121. 121. 
    Jeong Y, Rhee H, Martin S, Klass D, Lin Y et al. 2016. Identification and genetic manipulation of human and mouse oesophageal stem cells. Gut 65:1077–86
     [Google Scholar]
  122. 122. 
    Kalabis J, Oyama K, Okawa T, Nakagawa H, Michaylira CZ et al. 2008. A subpopulation of mouse esophageal basal cells has properties of stem cells with the capacity for self-renewal and lineage specification. J. Clin. Investig. 118:3860–69
     [Google Scholar]
  123. 123. 
    Pan Q, Nicholson AM, Barr H, Harrison LA, Wilson GD et al. 2013. Identification of lineage-uncommitted, long-lived, label-retaining cells in healthy human esophagus and stomach, and in metaplastic esophagus. Gastroenterology 144:761–70
     [Google Scholar]
  124. 124. 
    DeWard AD, Cramer J, Lagasse E 2014. Cellular heterogeneity in the mouse esophagus implicates the presence of a nonquiescent epithelial stem cell population. Cell Rep 9:701–11
     [Google Scholar]
  125. 125. 
    Doupe DP, Alcolea MP, Roshan A, Zhang G, Klein AM et al. 2012. A single progenitor population switches behavior to maintain and repair esophageal epithelium. Science 337:1091–93
     [Google Scholar]
  126. 126. 
    Mills JC, Shivdasani RA. 2011. Gastric epithelial stem cells. Gastroenterology 140:412–24
     [Google Scholar]
  127. 127. 
    Bjerknes M, Cheng H. 2002. Multipotential stem cells in adult mouse gastric epithelium. Am. J. Physiol. Gastrointest. Liver Physiol. 283:G767–77
     [Google Scholar]
  128. 128. 
    Lee ER, Leblond CP. 1985. Dynamic histology of the antral epithelium in the mouse stomach: II. Ultrastructure and renewal of isthmal cells. Am. J. Anat. 172:205–24
     [Google Scholar]
  129. 129. 
    Qiao XT, Ziel JW, McKimpson W, Madison BB, Todisco A et al. 2007. Prospective identification of a multilineage progenitor in murine stomach epithelium. Gastroenterology 133:1989–98
     [Google Scholar]
  130. 130. 
    Barker N, Huch M, Kujala P, van de Wetering M, Snippert HJ et al. 2010. Lgr5+ve stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell 6:25–36
     [Google Scholar]
  131. 131. 
    Arnold K, Sarkar A, Yram MA, Polo JM, Bronson R et al. 2011. Sox2+ adult stem and progenitor cells are important for tissue regeneration and survival of mice. Cell Stem Cell 9:317–29
     [Google Scholar]
  132. 132. 
    Stange DE, Koo BK, Huch M, Sibbel G, Basak O et al. 2013. Differentiated Troy+ chief cells act as reserve stem cells to generate all lineages of the stomach epithelium. Cell 155:357–68
     [Google Scholar]
  133. 133. 
    Nam KT, Lee HJ, Sousa JF, Weis VG, O'Neal RL et al. 2010. Mature chief cells are cryptic progenitors for metaplasia in the stomach. Gastroenterology 139:2028–37.e9
     [Google Scholar]
  134. 134. 
    Walker MR, Patel KK, Stappenbeck TS 2009. The stem cell niche. J. Pathol. 217:169–80
     [Google Scholar]
  135. 135. 
    Santos AJM, Lo YH, Mah AT, Kuo CJ 2018. The intestinal stem cell niche: homeostasis and adaptations. Trends Cell Biol 28:1062–78
     [Google Scholar]
  136. 136. 
    van de Wetering M, Sancho E, Verweij C, de Lau W, Oving I et al. 2002. The β-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 111:241–50
     [Google Scholar]
  137. 137. 
    Kosinski C, Li VS, Chan AS, Zhang J, Ho C et al. 2007. Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors. PNAS 104:15418–23
     [Google Scholar]
  138. 138. 
    Korinek V, Barker N, Moerer P, van Donselaar E, Huls G et al. 1998. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nat. Genet. 19:379–83
     [Google Scholar]
  139. 139. 
    Fevr T, Robine S, Louvard D, Huelsken J 2007. Wnt/β-catenin is essential for intestinal homeostasis and maintenance of intestinal stem cells. Mol. Cell Biol. 27:7551–59
     [Google Scholar]
  140. 140. 
    Pinto D, Gregorieff A, Begthel H, Clevers H 2003. Canonical Wnt signals are essential for homeostasis of the intestinal epithelium. Genes Dev 17:1709–13
     [Google Scholar]
  141. 141. 
    Kuhnert F, Davis CR, Wang HT, Chu P, Lee M et al. 2004. Essential requirement for Wnt signaling in proliferation of adult small intestine and colon revealed by adenoviral expression of Dickkopf-1. PNAS 101:266–71
     [Google Scholar]
  142. 142. 
    Muncan V, Sansom OJ, Tertoolen L, Phesse TJ, Begthel H et al. 2006. Rapid loss of intestinal crypts upon conditional deletion of the Wnt/Tcf-4 target gene c-Myc. Mol. Cell. Biol 26:8418–26
     [Google Scholar]
  143. 143. 
    Schepers A, Clevers H. 2012. Wnt signaling, stem cells, and cancer of the gastrointestinal tract. Cold Spring Harb. Perspect. Biol. 4:a007989
     [Google Scholar]
  144. 144. 
    Andreu P, Colnot S, Godard C, Gad S, Chafey P et al. 2005. Crypt-restricted proliferation and commitment to the Paneth cell lineage following Apc loss in the mouse intestine. Development 132:1443–51
     [Google Scholar]
  145. 145. 
    van Es JH, Jay P, Gregorieff A, van Gijn ME, Jonkheer S et al. 2005. Wnt signalling induces maturation of Paneth cells in intestinal crypts. Nat. Cell Biol. 7:381–86
     [Google Scholar]
  146. 146. 
    Bastide P, Darido C, Pannequin J, Kist R, Robine S et al. 2007. Sox9 regulates cell proliferation and is required for Paneth cell differentiation in the intestinal epithelium. J. Cell Biol. 178:635–48
     [Google Scholar]
  147. 147. 
    Mori-Akiyama Y, van den Born M, van Es JH, Hamilton SR, Adams HP et al. 2007. SOX9 is required for the differentiation of Paneth cells in the intestinal epithelium. Gastroenterology 133:539–46
     [Google Scholar]
  148. 148. 
    Batlle E, Henderson JT, Beghtel H, van den Born MM, Sancho E et al. 2002. β-Catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. Cell 111:251–63
     [Google Scholar]
  149. 149. 
    van der Flier LG, Clevers H 2009. Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu. Rev. Physiol. 71:241–60
     [Google Scholar]
  150. 150. 
    Hardwick JC, Van Den Brink GR, Bleuming SA, Ballester I, Van Den Brande JM et al. 2004. Bone morphogenetic protein 2 is expressed by, and acts upon, mature epithelial cells in the colon. Gastroenterology 126:111–21
     [Google Scholar]
  151. 151. 
    Haramis AP, Begthel H, van den Born M, van Es J, Jonkheer S et al. 2004. De novo crypt formation and juvenile polyposis on BMP inhibition in mouse intestine. Science 303:1684–86
     [Google Scholar]
  152. 152. 
    He XC, Zhang J, Tong WG, Tawfik O, Ross J et al. 2004. BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-β-catenin signaling. Nat. Genet. 36:1117–21
     [Google Scholar]
  153. 153. 
    Milano J, McKay J, Dagenais C, Foster-Brown L, Pognan F et al. 2004. Modulation of notch processing by γ-secretase inhibitors causes intestinal goblet cell metaplasia and induction of genes known to specify gut secretory lineage differentiation. Toxicol. Sci. 82:341–58
     [Google Scholar]
  154. 154. 
    Wong GT, Manfra D, Poulet FM, Zhang Q, Josien H et al. 2004. Chronic treatment with the γ-secretase inhibitor LY-411,575 inhibits β-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. J. Biol. Chem. 279:12876–82
     [Google Scholar]
  155. 155. 
    van Es JH, van Gijn ME, Riccio O, van den Born M, Vooijs M et al. 2005. Notch/γ-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature 435:959–63
     [Google Scholar]
  156. 156. 
    Tian H, Biehs B, Chiu C, Siebel CW, Wu Y et al. 2015. Opposing activities of Notch and Wnt signaling regulate intestinal stem cells and gut homeostasis. Cell Rep 11:33–42
     [Google Scholar]
  157. 157. 
    Fre S, Huyghe M, Mourikis P, Robine S, Louvard D, Artavanis-Tsakonas S 2005. Notch signals control the fate of immature progenitor cells in the intestine. Nature 435:964–68
     [Google Scholar]
  158. 158. 
    von Rahden BH, Kircher S, Lazariotou M, Reiber C, Stuermer L et al. 2011. LgR5 expression and cancer stem cell hypothesis: clue to define the true origin of esophageal adenocarcinomas with and without Barrett's Esophagus. J. Exp. Clin. Cancer Res. 30:23
     [Google Scholar]
  159. 159. 
    Hoffmann JA. 2003. The immune response of Drosophila. Nature 426:33–38
     [Google Scholar]
  160. 160. 
    de Jong HK, Parry CM, van der Poll T, Wiersinga WJ 2012. Host-pathogen interaction in invasive Salmonellosis. PLOS Pathog 8:e1002933
     [Google Scholar]
  161. 161. 
    Meylan F, Richard AC, Siegel RM 2011. TL1A and DR3, a TNF family ligand-receptor pair that promotes lymphocyte costimulation, mucosal hyperplasia, and autoimmune inflammation. Immunol. Rev. 244:188–96
     [Google Scholar]
  162. 162. 
    Xavier RJ, Podolsky DK. 2007. Unravelling the pathogenesis of inflammatory bowel disease. Nature 448:427–34
     [Google Scholar]
  163. 163. 
    Pasparakis M. 2012. Role of NF-κB in epithelial biology. Immunol. Rev. 246:346–58
     [Google Scholar]
  164. 164. 
    Wullaert A, Bonnet MC, Pasparakis M 2011. NF-κB in the regulation of epithelial homeostasis and inflammation. Cell Res 21:146–58
     [Google Scholar]
  165. 165. 
    Lindemans CA, Calafiore M, Mertelsmann AM, O'Connor MH, Dudakov JA et al. 2015. Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration. Nature 528:560–64
     [Google Scholar]
  166. 166. 
    Mizoguchi A, Yano A, Himuro H, Ezaki Y, Sadanaga T, Mizoguchi E 2018. Clinical importance of IL-22 cascade in IBD. J. Gastroenterol. 53:465–74
     [Google Scholar]
  167. 167. 
    Rangan P, Choi I, Wei M, Navarrete G, Guen E et al. 2019. Fasting-mimicking diet modulates microbiota and promotes intestinal regeneration to reduce inflammatory bowel disease pathology. Cell Rep 26:2704–19.e6
     [Google Scholar]
  168. 168. 
    Yilmaz ÖH, Katajisto P, Lamming DW, Gültekin Y, Bauer-Rowe KE et al. 2012. mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake. Nature 486:490–95
     [Google Scholar]
  169. 169. 
    Beyaz S, Mana MD, Roper J, Kedrin D, Saadatpour A et al. 2016. High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature 531:53–58
     [Google Scholar]
  170. 170. 
    Mihaylova MM, Cheng CW, Cao AQ, Tripathi S, Mana MD et al. 2018. Fasting activates fatty acid oxidation to enhance intestinal stem cell function during homeostasis and aging. Cell Stem Cell 22:769–78.e4
     [Google Scholar]
  171. 171. 
    Thaiss CA, Levy M, Grosheva I, Zheng D, Soffer E et al. 2018. Hyperglycemia drives intestinal barrier dysfunction and risk for enteric infection. Science 359:1376–83
     [Google Scholar]
  172. 172. 
    Martin K, Potten CS, Roberts SA, Kirkwood TB 1998. Altered stem cell regeneration in irradiated intestinal crypts of senescent mice. J. Cell Sci. 111:Part 162297–303
     [Google Scholar]
  173. 173. 
    Nalapareddy K, Choudhury AR, Gompf A, Ju Z, Ravipati S et al. CHK2-independent induction of telomere dysfunction checkpoints in stem and progenitor cells. EMBO Rep 11:619–25
     [Google Scholar]
  174. 174. 
    Jurk D, Wilson C, Passos JF, Oakley F, Correia-Melo C et al. 2014. Chronic inflammation induces telomere dysfunction and accelerates ageing in mice. Nat. Commun. 2:4172
     [Google Scholar]
  175. 175. 
    Thevaranjan N, Puchta A, Schulz C, Naidoo A, Szamosi JC et al. 2017. Age-associated microbial dysbiosis promotes intestinal permeability, systemic inflammation, and macrophage dysfunction. Cell Host Microbe 21:455–66.e4
     [Google Scholar]
  176. 176. 
    Nalapareddy K, Nattamai KJ, Kumar RS, Karns R, Wikenheiser-Brokamp KA et al. 2017. Canonical Wnt signaling ameliorates aging of intestinal stem cells. Cell Rep 18:2608–21
     [Google Scholar]
  177. 177. 
    Kozar S, Morrissey E, Nicholson AM, van der Heijden M, Zecchini HI et al. 2013. Continuous clonal labeling reveals small numbers of functional stem cells in intestinal crypts and adenomas. Cell Stem Cell 13:626–33
     [Google Scholar]
  178. 178. 
    Pentinmikko N, Iqbal S, Mana M, Andersson S, Cognetta AB 3rd et al. 2019. Notum produced by Paneth cells attenuates regeneration of aged intestinal epithelium. Nature 571:398–402
     [Google Scholar]
  179. 179. 
    Moorefield EC, Andres SF, Blue RE, Van Landeghem L, Mah AT et al. 2017. Aging effects on intestinal homeostasis associated with expansion and dysfunction of intestinal epithelial stem cells. Aging 9:1898–915
     [Google Scholar]
  180. 180. 
    Cui H, Tang D, Garside GB, Zeng T, Wang Y et al. 2019. Wnt signaling mediates the aging-induced differentiation impairment of intestinal stem cells. Stem Cell Rev 15:448–55
     [Google Scholar]
  181. 181. 
    Radtke F, Clevers H. 2005. Self-renewal and cancer of the gut: two sides of a coin. Science 307:1904–9
     [Google Scholar]
  182. 182. 
    Tao Y, Kang B, Petkovich DA, Bhandari YR, In J et al. 2019. Aging-like spontaneous epigenetic silencing facilitates Wnt activation, stemness, and BrafV600E-induced tumorigenesis. Cancer Cell 35:315–28.e6
     [Google Scholar]
  183. 183. 
    Yousefi M, Nakauka-Ddamba A, Berry CT, Li N, Schoenberger J et al. 2018. Calorie restriction governs intestinal epithelial regeneration through cell-autonomous regulation of mTORC1 in reserve stem cells. Stem Cell Rep 10:703–11
     [Google Scholar]
  184. 184. 
    Rodgers JT, King KY, Brett JO, Cromie MJ, Charville GW et al. 2014. mTORC1 controls the adaptive transition of quiescent stem cells from G0 to GAlert. Nature 510:393–96
     [Google Scholar]
  185. 185. 
    Igarashi M, Miura M, Williams E, Jaksch F, Kadowaki T et al. 2019. NAD+ supplementation rejuvenates aged gut adult stem cells. Aging Cell 18:e12935
     [Google Scholar]
  186. 186. 
    Choi J, Rakhilin N, Gadamsetty P, Joe DJ, Tabrizian T et al. 2018. Intestinal crypts recover rapidly from focal damage with coordinated motion of stem cells that is impaired by aging. Sci. Rep. 8:10989
     [Google Scholar]
/content/journals/10.1146/annurev-physiol-021119-034359
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Intestinal Stem Cell Aging: Origins and Interventions
Annual Review of Physiology 82, 203 (2020); https://doi.org/10.1146/annurev-physiol-021119-034359
/content/journals/10.1146/annurev-physiol-021119-034359
/content/journals/10.1146/annurev-physiol-021119-034359
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