Generating human intestinal tissues from pluripotent stem cells to study development and disease

EMBO Journal

Volumn 34, Issue 9, 2015, Pages 1149-1163

  Sinagoga, Katie L ^a   Wells, James M ^a  

^a CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

Author keywords

endoderm; intestinal development; organoids; stem cells; tissue engineering

Indexed keywords

CELL DIFFERENTIATION; CELL FUNCTION; CELL INTERACTION; CELL MATURATION; CYTOPLASM; EMBRYONIC STEM CELL; ENDOCRINE FUNCTION; ENDODERM; ENTEROENDOCRINE CELL; ENTEROPATHY; GENETIC DISORDER; HUMAN; HUMAN INTESTINAL ORGANOID; IMMATURITY; IN VITRO STUDY; IN VIVO STUDY; INFECTION COMPLICATION; INTESTINAL STEM CELL; INTESTINE; INTESTINE CELL; INTESTINE EPITHELIUM CELL; INTESTINE FLORA; INTESTINE FUNCTION; INTESTINE INNERVATION; MORPHOGENESIS; NONHUMAN; PATHOPHYSIOLOGY; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; REVIEW; STEM CELL CULTURE; STEM CELL NICHE; TISSUE ENGINEERING; ANIMAL; CYTOLOGY; GENETICS; METABOLISM; MICROBIOLOGY; ORGAN CULTURE TECHNIQUE; PHYSIOLOGY; PROCEDURES;

ANIMALS; CELL DIFFERENTIATION; ENDODERM; HUMANS; INTESTINAL DISEASES; INTESTINES; ORGAN CULTURE TECHNIQUES; ORGANOIDS; PLURIPOTENT STEM CELLS; TISSUE ENGINEERING;

EID: 84929028894     PISSN: 02614189     EISSN: 14602075     Source Type: Journal    
DOI: 10.15252/embj.201490686     Document Type: Review

References (149)

1. Andrews ZB, (2011) Central mechanisms involved in the orexigenic actions of ghrelin. Peptides 32: 2248-2255
2. Antonica F, Kasprzyk DF, Opitz R, Iacovino M, Liao X-H, Dumitrescu AM, Refetoff S, Peremans K, Manto M, Kyba M, Costagliola S, (2012) Generation of functional thyroid from embryonic stem cells. Nature 491: 66-71
3. Bastide P, Darido C, Pannequin J, Kist R, Robine S, Marty-Double C, Bibeau F, Scherer G, Joubert D, Hollande F, Blache P, Jay P, (2007) Sox9 regulates cell proliferation and is required for Paneth cell differentiation in the intestinal epithelium. J Cell Biol 178: 635-648
4. Bauer E, Williams BA, Smidt H, Verstegen MWA, Mosenthin R, (2006) Influence of the gastrointestinal microbiota on development of the immune system in young animals. Curr Issues Intest Microbiol 7: 35-51
5. Bayha E, Jørgensen MC, Serup P, Grapin-Botton A, (2009) Retinoic acid signaling organizes endodermal organ specification along the entire antero-posterior axis. PLoS ONE 4: e5845
6. Bel-Vialar S, Itasaki N, Krumlauf R, (2002) Initiating Hox gene expression: in the early chick neural tube differential sensitivity to FGF and RA signaling subdivides the HoxB genes in two distinct groups. Development 129: 5103-5115
7. Beucher A, Gjernes E, Collin C, Courtney M, Meunier A, Collombat P, Gradwohl G, (2012) The homeodomain-containing transcription factors Arx and Pax4 control enteroendocrine subtype specification in mice. PLoS ONE 7: e36449
8. Bondurand N, Natarajan D, Thapar N, Atkins C, Pachnis V, (2003) Neuron and glia generating progenitors of the mammalian enteric nervous system isolated from foetal and postnatal gut cultures. Development 130: 6387-6400
9. Burns RC, Fairbanks TJ, Sala F, De Langhe S, Mailleux A, Thiery JP, Dickson C, Itoh N, Warburton D, Anderson KD, Bellusci S, (2004) Requirement for fibroblast growth factor 10 or fibroblast growth factor receptor 2-IIIb signaling for cecal development in mouse. Dev Biol 265: 61-74
10. Cacalano G, Fariñas I, Wang LC, Hagler K, Forgie A, Moore M, Armanini M, Phillips H, Ryan AM, Reichardt LF, Hynes M, Davies A, Rosenthal A, (1998) GFRalpha1 is an essential receptor component for GDNF in the developing nervous system and kidney. Neuron 21: 53-62
11. Cai J, Zhao Y, Liu Y, Ye F, Song Z, Qin H, Meng S, Chen Y, Zhou R, Song X, Guo Y, Ding M, Deng H, (2007) Directed differentiation of human embryonic stem cells into functional hepatic cells. Hepatology 45: 1229-1239
12. Cantrell VA, Owens SE, Chandler RL, Airey DC, Bradley KM, Smith JR, Southard-Smith EM, (2004) Interactions between Sox10 and EdnrB modulate penetrance and severity of aganglionosis in the Sox10Dom mouse model of Hirschsprung disease. Hum Mol Genet 13: 2289-2301
13. Cao L, Gibson JD, Miyamoto S, Sail V, Verma R, Rosenberg DW, Nelson CE, Giardina C, (2011) Intestinal lineage commitment of embryonic stem cells. Differentiation 81: 1-10
14. Cervantes S, Yamaguchi TP, Hebrok M, (2009) Wnt5a is essential for intestinal elongation in mice. Dev Biol 326: 285-294
15. Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L, (2009) Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 27: 275-280
16. Chen AE, Borowiak M, Sherwood RI, Kweudjeu A, Melton DA, (2013) Functional evaluation of ES cell-derived endodermal populations reveals differences between Nodal and Activin A-guided differentiation. Development 140: 675-686
17. Chen C, Fang R, Davis C, Maravelias C, Sibley E, (2009) Pdx1 inactivation restricted to the intestinal epithelium in mice alters duodenal gene expression in enterocytes and enteroendocrine cells. Am J Physiol Gastrointest Liver Physiol 297: G1126-G1137
18. Chen Y-J, Finkbeiner SR, Weinblatt D, Emmett MJ, Tameire F, Yousefi M, Yang C, Maehr R, Zhou Q, Shemer R, Dor Y, Li C, Spence JR, Stanger BZ, (2014) De novo formation of insulin-producing "neo-β cell islets" from intestinal crypts. Cell Rep 6: 1046-1058
19. Cheng H, Leblond CP, (1974) Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine I. Columnar cell. Am J Anat 141: 461-479
20. Cheng K, Samimi R, Xie G, Shant J, Drachenberg C, Wade M, Davis RJ, Nomikos G, Raufman J-P, (2008) Acetylcholine release by human colon cancer cells mediates autocrine stimulation of cell proliferation. Am J Physiol Gastrointest Liver Physiol 295: G591-G597
21. Crespo MA, González ML, Lozano MG, Paz SF, Pérez MR, Gago EV, Ferrer FM, (2009) Gastrointestinal hormones in food intake control. Endocrinol Nutr 56: 317-330
22. D'Amour KA, Agulnick AD, Eliazer S, Kelly OG, Kroon E, Baetge EE, (2005) Efficient differentiation of human embryonic stem cells to definitive endoderm. Nat Biotechnol 23: 1534-1541
23. D'Amour KA, Bang AG, Eliazer S, Kelly OG, Agulnick AD, Smart NG, Moorman MA, Kroon E, Carpenter MK, Baetge EE, (2006) Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotechnol 24: 1392-1401
24. De La Serre CB, Ellis CL, Lee J, Hartman AL, Rutledge JC, Raybould HE, (2010) Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation. Am J Physiol Gastrointest Liver Physiol 299: G440-G448
25. Deacon CF, Ahrén B, (2011) Physiology of incretins in health and disease. Rev Diabet Stud 8: 293-306
26. Dekkers JF, Wiegerinck CL, de Jonge HR, Bronsveld I, Janssens HM, de Winter-de Groot KM, Brandsma AM, de Jong NWM, Bijvelds MJC, Scholte BJ, Nieuwenhuis EES, van den Brink S, Clevers H, van der Ent CK, Middendorp S, Beekman JM, (2013) A functional CFTR assay using primary cystic fibrosis intestinal organoids. Nat Med 19: 939-945
27. Desai S, Loomis Z, Pugh-Bernard A, Schrunk J, Doyle MJ, Minic A, McCoy E, Sussel L, (2008) Nkx2.2 regulates cell fate choice in the enteroendocrine cell lineages of the intestine. Dev Biol 313: 58-66
28. Dessimoz J, Opoka R, Kordich JJ, Grapin-Botton A, Wells JM, (2006) FGF signaling is necessary for establishing gut tube domains along the anterior-posterior axis in vivo. Mech Dev 123: 42-55
29. Dupin E, Sommer L, (2012) Neural crest progenitors and stem cells: from early development to adulthood. Dev Biol 366: 83-95
30. Eberhard ML, Pieniazek NJ, Arrowood MJ, (1997) Laboratory diagnosis of Cyclospora infections. Arch Pathol Lab Med 121: 792-797
31. Eberl G, Lochner M, (2009) The development of intestinal lymphoid tissues at the interface of self and microbiota. Mucosal Immunol 2: 478-485
32. Ehrman LA, Yutzey KE, (2001) Anterior expression of the caudal homologue cCdx-B activates a posterior genetic program in avian embryos. Dev Dyn 221: 412-421
33. Finkbeiner SR, Zeng X-L, Utama B, Atmar RL, Shroyer NF, Estes MK, (2012) Stem cell-derived human intestinal organoids as an infection model for rotaviruses. MBio 3: e00159-12
34. Flamant M, Aubert P, Rolli-Derkinderen M, Bourreille A, Neunlist MR, Mahé MM, Meurette G, Marteyn B, Savidge T, Galmiche JP, Sansonetti PJ, Neunlist M, (2011) Enteric glia protect against Shigella flexneri invasion in intestinal epithelial cells: a role for S-nitrosoglutathione. Gut 60: 473-484
35. Fordham RP, Yui S, Hannan NRF, Soendergaard C, Madgwick A, Schweiger PJ, Nielsen OH, Vallier L, Pedersen RA, Nakamura T, Watanabe M, Jensen KB, (2013) Transplantation of expanded fetal intestinal progenitors contributes to colon regeneration after injury. Cell Stem Cell 13: 734-744
36. 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: 964-968
37. Gerbe F, Legraverend C, Jay P, (2012) The intestinal epithelium tuft cells: specification and function. Cell Mol Life Sci 69: 2907-2917
38. Gianino S, Grider JR, Cresswell J, Enomoto H, Heuckeroth RO, (2003) GDNF availability determines enteric neuron number by controlling precursor proliferation. Development 130: 2187-2198
39. Gibbons DL, Spencer J, (2011) Mouse and human intestinal immunity: same ballpark, different players; different rules, same score. Mucosal Immunol 4: 148-157
40. Goldstein AM, Hofstra RMW, Burns AJ, (2013) Building a brain in the gut: development of the enteric nervous system. Clin Genet 83: 307-316
41. Goode T, O'Connor T, Hopkins A, Moriarty D, O'Sullivan GC, Collins JK, O'Donoghue D, Baird AW, O'Connell J, Shanahan F, (2003) Neurokinin-1 receptor (NK-1R) expression is induced in human colonic epithelial cells by proinflammatory cytokines and mediates proliferation in response to substance P. J Cell Physiol 197: 30-41
42. Grainger S, Savory JGA, Lohnes D, (2010) Cdx2 regulates patterning of the intestinal epithelium. Dev Biol 339: 155-165
43. Gregorieff A, Grosschedl R, Clevers H, (2004) Hindgut defects and transformation of the gastro-intestinal tract in Tcf4(-/-)/Tcf1(-/-) embryos. EMBO J 23: 1825-1833
44. Grosse AS, Pressprich MF, Curley LB, Hamilton KL, Margolis B, Hildebrand JD, Gumucio DL, (2011) Cell dynamics in fetal intestinal epithelium: implications for intestinal growth and morphogenesis. Development 138: 4423-4432
45. Halliez MCM, Buret AG, (2013) Extra-intestinal and long term consequences of Giardia duodenalis infections. World J Gastroenterol 19: 8974-8985
46. Han J-L, Lin H-L, (2014) Intestinal microbiota and type 2 diabetes: from mechanism insights to therapeutic perspective. World J Gastroenterol 20: 17737-17745
47. Hatch J, Mukouyama Y-S, (2014) Spatiotemporal mapping of vascularization and innervation in the fetal murine intestine. Dev Dyn 244: 56-68
48. Ho CY, Houart C, Wilson SW, Stainier DY, (1999) A role for the extraembryonic yolk syncytial layer in patterning the zebrafish embryo suggested by properties of the hex gene. Curr Biol 9: 1131-1134
49. Hounnou G, Destrieux C, Desmé J, Bertrand P, Velut S, (2002) Anatomical study of the length of the human intestine. Surg Radiol Anat 24: 290-294
50. Huang D, Chen SW, Langston AW, Gudas LJ, (1998) A conserved retinoic acid responsive element in the murine Hoxb-1 gene is required for expression in the developing gut. Development 125: 3235-3246
51. Huizinga JD, Chen J-H, (2014) Interstitial cells of Cajal: update on basic and clinical science. Curr Gastroenterol Rep 16: 363
52. Jenny M, Uhl C, Roche C, Duluc I, Guillermin V, Guillemot F, Jensen J, Kedinger M, Gradwohl G, (2002) Neurogenin3 is differentially required for endocrine cell fate specification in the intestinal and gastric epithelium. EMBO J 21: 6338-6347
53. Jensen J, Pedersen EE, Galante P, Hald J, Heller RS, Ishibashi M, Kageyama R, Guillemot F, Serup P, Madsen OD, (2000) Control of endodermal endocrine development by Hes-1. Nat Genet 24: 36-44
54. Kapur RP, (1999) Early death of neural crest cells is responsible for total enteric aganglionosis in Sox10(Dom)/Sox10(Dom) mouse embryos. Pediatr Dev Pathol 2: 559-569
55. Karlsson L, Lindahl P, Heath JK, Betsholtz C, (2000) Abnormal gastrointestinal development in PDGF-A and PDGFR-(alpha) deficient mice implicates a novel mesenchymal structure with putative instructive properties in villus morphogenesis. Development 127: 3457-3466
56. Katz JP, Perreault N, Goldstein BG, Lee CS, Labosky PA, Yang VW, Kaestner KH, (2002) The zinc-finger transcription factor Klf4 is required for terminal differentiation of goblet cells in the colon. Development 129: 2619-2628
57. Kinkel MD, Eames SC, Alonzo MR, Prince VE, (2008) Cdx4 is required in the endoderm to localize the pancreas and limit beta-cell number. Development 135: 919-929
58. Krause WJ, (2000) Brunner's glands: a structural, histochemical and pathological profile. Prog Histochem Cytochem 35: 255-367
59. Kreitzer FR, Salomonis N, Sheehan A, Huang M, Park JS, Spindler MJ, Lizarraga P, Weiss WA, So P-L, Conklin BR, (2013) A robust method to derive functional neural crest cells from human pluripotent stem cells. Am J Stem Cells 2: 119-131
60. Kubo A, Shinozaki K, Shannon JM, Kouskoff V, Kennedy M, Woo S, Fehling HJ, Keller G, (2004) Development of definitive endoderm from embryonic stem cells in culture. Development 131: 1651-1662
61. Kumar M, Jordan N, Melton D, Grapin-Botton A, (2003) Signals from lateral plate mesoderm instruct endoderm toward a pancreatic fate. Dev Biol 259: 109-122
62. Lake JI, Heuckeroth RO, (2013) Enteric nervous system development: migration, differentiation, and disease. Am J Physiol Gastrointest Liver Physiol 305: G1-G24
63. Lancaster MA, Knoblich JA, (2014) Organogenesis in a dish: modeling development and disease using organoid technologies. Science 345: 1247125
64. Larsson L-I, St-Onge L, Hougaard DM, Sosa-Pineda B, Gruss P, (1998) Pax 4 and 6 regulate gastrointestinal endocrine cell development. Mech Dev 79: 153-159
65. Leslie JL, Huang S, Opp JS, Nagy MS, Kobayashi M, Young VB, Spence JR, (2014) Persistence and toxin production by Clostridium difficile within human intestinal organoids results in disruption of epithelial paracellular barrier function. Infect Immun 83: 138-145
66. Li J, Butcher J, Mack D, Stintzi A, (2014a) Functional Impacts of the Intestinal Microbiome in the Pathogenesis of Inflammatory Bowel Disease. Inflamm Bowel Dis 29: 107-114
67. Li X, Nadauld L, Ootani A, Corney DC, Pai RK, Gevaert O, Cantrell MA, Rack PG, Neal JT, Chan CW-M, Yeung T, Gong X, Yuan J, Wilhelmy J, Robine S, Attardi LD, Plevritis SK, Hung KE, Chen C-Z, Ji HP, et al, (2014b) Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture. Nat Med 20: 769-777
68. Li Y, (2007) Sensory signal transduction in the vagal primary afferent neurons. Curr Med Chem 14: 2554-2563
69. Lickert H, Kemler R, (2002) Functional analysis of cis-regulatory elements controlling initiation and maintenance of early Cdx1 gene expression in the mouse. Dev Dyn 225: 216-220
70. Longmire TA, Ikonomou L, Hawkins F, Christodoulou C, Cao Y, Jean JC, Kwok LW, Mou H, Rajagopal J, Shen SS, Dowton AA, Serra M, Weiss DJ, Green MD, Snoeck H-W, Ramirez MI, Kotton DN, (2012) Efficient derivation of purified lung and thyroid progenitors from embryonic stem cells. Cell Stem Cell 10: 398-411
71. Lõpez-Díaz L, Jain RN, Keeley TM, VanDussen KL, Brunkan CS, Gumucio DL, Samuelson LC, (2007) Intestinal Neurogenin 3 directs differentiation of a bipotential secretory progenitor to endocrine cell rather than goblet cell fate. Dev Biol 309: 298-305
72. Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R, (2012) Diversity, stability and resilience of the human gut microbiota. Nature 489: 220-230
73. Lumelsky N, Blondel O, Laeng P, Velasco I, Ravin R, McKay R, (2001) Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science 292: 1389-1394
74. Manié S, Santoro M, Fusco A, Billaud M, (2001) The RET receptor: function in development and dysfunction in congenital malformation. Trends Genet 17: 580-589
75. Mansfield LS, Gajadhar AA, (2004) Cyclospora cayetanensis, a food- and waterborne coccidian parasite. Vet Parasitol 126: 73-90
76. Mawe GM, Hoffman JM, (2013) Serotonin Signaling in the Gastrointestinal Tract: functions, dysfunctions, and therapeutic targets. Nat Rev Gastroenterol Hepatol 10: 473-486
77. McCracken KW, Catá EM, Crawford CM, Sinagoga KL, Schumacher M, Rockich BE, Tsai Y-H, Mayhew CN, Spence JR, Zavros Y, Wells JM, (2014) Modelling human development and disease in pluripotent stem-cell-derived gastric organoids. Nature 516: 400-404
78. McCracken KW, Howell JC, Wells JM, Spence JR, (2011) Generating human intestinal tissue from pluripotent stem cells in vitro. Nat Protoc 6: 1920-1928
79. McKeown SJ, Stamp L, Hao MM, Young HM, (2013) Hirschsprung disease: a developmental disorder of the enteric nervous system. Wiley Interdiscip Rev Dev Biol 2: 113-129
80. McLin VA, Rankin SA, Zorn AM, (2007) Repression of Wnt/beta-catenin signaling in the anterior endoderm is essential for liver and pancreas development. Development 134: 2207-2217
81. Menendez L, Kulik MJ, Page AT, Park SS, Lauderdale JD, Cunningham ML, Dalton S, (2013) Directed differentiation of human pluripotent cells to neural crest stem cells. Nat Protoc 8: 203-212
82. Menendez L, Yatskievych TA, Antin PB, Dalton S, (2011) Wnt signaling and a Smad pathway blockade direct the differentiation of human pluripotent stem cells to multipotent neural crest cells. Proc Natl Acad Sci USA 108: 19240-19245
83. Mooseker MS, (1985) Organization, chemistry, and assembly of the cytoskeletal apparatus of the intestinal brush border. Annu Rev Cell Biol 1: 209-241
84. Mori-Akiyama Y, van den Born M, van Es JH, Hamilton SR, Adams HP, Zhang J, Clevers H, de Crombrugghe B, (2007) SOX9 is required for the differentiation of paneth cells in the intestinal epithelium. Gastroenterology 133: 539-546
85. Mou H, Zhao R, Sherwood R, Ahfeldt T, Lapey A, Wain J, Sicilian L, Izvolsky K, Musunuru K, Cowan C, Rajagopal J, (2012) Generation of multipotent lung and airway progenitors from mouse ESCs and patient-specific cystic fibrosis iPSCs. Cell Stem Cell 10: 385-397
86. Mummery C, Ward D, van den Brink CE, Bird SD, Doevendans PA, Opthof T, Brutel de la Riviere A, Tertoolen L, van der Heyden M, Pera M, (2002) Cardiomyocyte differentiation of mouse and human embryonic stem cells. J Anat 200: 233-242
87. Mustata RC, Vasile G, Fernandez-Vallone V, Strollo S, Lefort A, Libert F, Monteyne D, Pérez-Morga D, Vassart G, Garcia M-I, (2013) Identification of Lgr5-independent spheroid-generating progenitors of the mouse fetal intestinal epithelium. Cell Rep 5: 421-432
88. Nankervis CA, Giannone PJ, Reber KM, (2008) The neonatal intestinal vasculature: contributing factors to necrotizing enterocolitis. Semin Perinatol 32: 83-91
89. Natarajan D, Grigoriou M, Marcos-Gutierrez CV, Atkins C, Pachnis V, (1999) Multipotential progenitors of the mammalian enteric nervous system capable of colonising aganglionic bowel in organ culture. Development 126: 157-168
90. Nathan JD, Liddle RA, (2002) Neurohormonal control of pancreatic exocrine secretion. Curr Opin Gastroenterol 18: 536-544
91. Naya FJ, Huang HP, Qiu Y, Mutoh H, DeMayo FJ, Leiter AB, Tsai MJ, (1997) Diabetes, defective pancreatic morphogenesis, and abnormal enteroendocrine differentiation in BETA2/neuroD-deficient mice. Genes Dev 11: 2323-2334
92. Neunlist M, Van Landeghem L, Mahé MM, Derkinderen P, des Varannes SB, Rolli-Derkinderen M, (2013) The digestive neuronal-glial-epithelial unit: a new actor in gut health and disease. Nat Rev Gastroenterol Hepatol 10: 90-100
93. Niederreither K, Vermot J, Le Roux I, Schuhbaur B, Chambon P, Dollé P, (2003) The regional pattern of retinoic acid synthesis by RALDH2 is essential for the development of posterior pharyngeal arches and the enteric nervous system. Development 130: 2525-2534
94. Noah TK, Donahue B, Shroyer NF, (2011) Intestinal development and differentiation. Exp Cell Res 317: 2702-2710
95. Ootani A, Li X, Sangiorgi E, Ho QT, Ueno H, Toda S, Sugihara H, Fujimoto K, Weissman IL, Capecchi MR, Kuo CJ, (2009) Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche. Nat Med 15: 701-706
96. Pellegrinet L, Rodilla V, Liu Z, Chen S, Koch U, Espinosa L, Kaestner KH, Kopan R, Lewis J, Radtke F, (2011) Dll1- and dll4-mediated notch signaling are required for homeostasis of intestinal stem cells. Gastroenterology 140: 1230-1240.e7
97. Pinney SE, Oliver-Krasinski J, Ernst L, Hughes N, Patel P, Stoffers DA, Russo P, De Leõn DD, (2011) Neonatal diabetes and congenital malabsorptive diarrhea attributable to a novel mutation in the human neurogenin-3 gene coding sequence. J Clin Endocrinol Metab 96: 1960-1965
98. Pownall ME, Isaacs HV, Slack JM, (1998) Two phases of Hox gene regulation during early Xenopus development. Curr Biol 8: 673-676
99. Putignani L, Carsetti R, Signore F, Manco M, (2010) Additional maternal and nonmaternal factors contribute to microbiota shaping in newborns. Proc Natl Acad Sci USA 107: E159; author reply E160
100. Rankin SA, Kormish J, Kofron M, Jegga A, Zorn AM, (2011) A gene regulatory network controlling hhex transcription in the anterior endoderm of the organizer. Dev Biol 351: 297-310
101. Reinus JF, Simon D, (2014) Gastrointestinal Anatomy and Physiology: The Essentials. Oxford, UK: John Wiley & Sons, Ltd
102. Rindi G, Ratineau C, Ronco A, Candusso ME, Tsai M, Leiter AB, (1999) Targeted ablation of secretin-producing cells in transgenic mice reveals a common differentiation pathway with multiple enteroendocrine cell lineages in the small intestine. Development 4156: 4149-4156
103. Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N, Chou JL, (1989) Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245: 1066-1073
104. Roberts DJ, Johnson RL, Burke AC, Nelson CE, Morgan BA, Tabin C, (1995) Sonic hedgehog is an endodermal signal inducing Bmp-4 and Hox genes during induction and regionalization of the chick hindgut. Development 121: 3163-3174
105. Rubio-Cabezas O, Jensen JN, Hodgson MI, Codner E, Ellard S, Serup P, Hattersley AT, (2011) Permanent Neonatal Diabetes and Enteric Anendocrinosis Associated With Biallelic Mutations in NEUROG3. Diabetes 60: 1349-1353
106. Sala FG, Curtis JL, Veltmaat JM, Del Moral P-M, Le LT, Fairbanks TJ, Warburton D, Ford H, Wang K, Burns RC, Bellusci S, (2006) Fibroblast growth factor 10 is required for survival and proliferation but not differentiation of intestinal epithelial progenitor cells during murine colon development. Dev Biol 299: 373-385
107. Sato T, Clevers H, (2013) Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. Science 340: 1190-1194
108. Sato T, Stange DE, Ferrante M, Vries RGJ, Van Es JH, Van den Brink S, Van Houdt WJ, Pronk A, Van Gorp J, Siersema PD, Clevers H, (2011) Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium. Gastroenterology 141: 1762-1772
109. Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ, Clevers H, (2009) Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459: 262-265
110. Savioli L, Smith H, Thompson A, (2006) Giardia and Cryptosporidium join the "Neglected Diseases Initiative". Trends Parasitol 22: 203-208
111. Schuchardt A, D'Agati V, Larsson-Blomberg L, Costantini F, Pachnis V, (1994) Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature 367: 380-383
112. Sekirov I, Russell SL, Antunes LCM, Finlay BB, (2010) Gut microbiota in health and disease. Physiol Rev 90: 859-904
113. Sherwood R, (2009) Transcriptional dynamics of endodermal organ formation. Dev Dyn 238: 29-42
114. Shirahashi H, Wu J, Yamamoto N, Catana A, Wege H, Wager B, Okita K, Zern MA, (2004) Differentiation of human and mouse embryonic stem cells along a hepatocyte lineage. Cell Transplant 13: 197-211
115. Shroyer NF, Helmrath MA, Wang VY-C, Antalffy B, Henning SJ, Zoghbi HY, (2007) Intestine-specific ablation of mouse atonal homolog 1 (Math1) reveals a role in cellular homeostasis. Gastroenterology 132: 2478-2488
116. Shyer AE, Tallinen T, Nerurkar NL, Wei Z, Gil ES, Kaplan DL, Tabin CJ, Mahadevan L, (2013) Villification: how the gut gets its villi. Science 342: 212-218
117. Sinner D, Kirilenko P, Rankin S, Wei E, Howard L, Kofron M, Heasman J, Woodland HR, Zorn AM, (2006) Global analysis of the transcriptional network controlling Xenopus endoderm formation. Development 133: 1955-1966
118. Southard-Smith EM, Kos L, Pavan WJ, (1998) Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse model. Nat Genet 18: 60-64
119. Spence JR, Lauf R, Shroyer NF, (2011a) Vertebrate intestinal endoderm development. Dev Dyn 240: 501-520
120. Spence JR, Mayhew CN, Rankin SA, Kuhar MF, Vallance JE, Tolle K, Hoskins EE, Kalinichenko VV, Wells SI, Zorn AM, Shroyer NF, Wells JM, (2011b) Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 470: 105-109
121. Stafford D, Prince VE, (2002) Retinoic acid signaling is required for a critical early step in zebrafish pancreatic development. Curr Biol 12: 1215-1220
122. Stanger BZ, Datar R, Murtaugh LC, Melton DA, (2005) Direct regulation of intestinal fate by Notch. Proc Natl Acad Sci USA 102: 12443-12448
123. Strader AD, Woods SC, (2005) Gastrointestinal hormones and food intake. Gastroenterology 128: 175-191
124. Takebe T, Sekine K, Enomura M, Koike H, Kimura M, Ogaeri T, Zhang R-R, Ueno Y, Zheng Y-W, Koike N, Aoyama S, Adachi Y, Taniguchi H, (2013) Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 499: 481-484
125. Talchai C, Xuan S, Kitamura T, DePinho RA, Accili D, (2012) Generation of functional insulin-producing cells in the gut by Foxo1 ablation. Nat Genet 44: 406-412, S1
126. Tiso N, Filippi A, Pauls S, Bortolussi M, Argenton F, (2002) BMP signalling regulates anteroposterior endoderm patterning in zebrafish. Mech Dev 118: 29-37
127. Toumi F, Neunlist M, Cassagnau E, Parois S, Laboisse CL, Galmiche J-P, Jarry A, (2003) Human submucosal neurones regulate intestinal epithelial cell proliferation: evidence from a novel co-culture model. Neurogastroenterol Motil 15: 239-242
128. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI, (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444: 1027-1031
129. Underwood MA, (2012) Paneth cells and necrotizing enterocolitis. Gut Microbes 3: 562-565
130. Van Landeghem L, Chevalier J, Mahé MM, Wedel T, Urvil P, Derkinderen P, Savidge T, Neunlist M, (2011) Enteric glia promote intestinal mucosal healing via activation of focal adhesion kinase and release of proEGF. Am J Physiol Gastrointest Liver Physiol 300: G976-G987
131. Walton KD, Kolterud A, Czerwinski MJ, Bell MJ, Prakash A, Kushwaha J, Grosse AS, Schnell S, Gumucio DL, (2012) Hedgehog-responsive mesenchymal clusters direct patterning and emergence of intestinal villi. Proc Natl Acad Sci USA 109: 15817-15822
132. Wang J, Cortina G, Wu SV, Tran R, Cho J-H, Tsai M-J, Bailey TJ, Jamrich M, Ament ME, Treem WR, Hill ID, Vargas JH, Gershman G, Farmer DG, Reyen L, Martín MG, (2006a) Mutant neurogenin-3 in congenital malabsorptive diarrhea. N Engl J Med 355: 270-280
133. Wang Y-C, Gallego-Arteche E, Iezza G, Yuan X, Matli MR, Choo S-P, Zuraek MB, Gogia R, Lynn FC, German MS, Bergsland EK, Donner DB, Warren RS, Nakakura EK, (2009) Homeodomain transcription factor NKX2.2 functions in immature cells to control enteroendocrine differentiation and is expressed in gastrointestinal neuroendocrine tumors. Endocr Relat Cancer 16: 267-279
134. Wang Z, Dollé P, Cardoso WV, Niederreither K, (2006b) Retinoic acid regulates morphogenesis and patterning of posterior foregut derivatives. Dev Biol 297: 433-445
135. Wang Z-K, (2014) Intestinal microbiota pathogenesis and fecal microbiota transplantation for inflammatory bowel disease. World J Gastroenterol 20: 14805
136. Watson CL, Mahe MM, Múnera J, Howell JC, Sundaram N, Poling HM, Schweitzer JI, Vallance JE, Mayhew CN, Sun Y, Grabowski G, Finkbeiner SR, Spence JR, Shroyer NF, Wells JM, Helmrath MA, (2014) An in vivo model of human small intestine using pluripotent stem cells. Nat Med 20: 1310-1314
137. Wells JM, Melton DA, (2000) Early mouse endoderm is patterned by soluble factors from adjacent germ layers. Development 1572: 1563-1572
138. World Health Organization (2004) WHO guidelines for drinking-water quality. Geneva: World Health Organization
139. Wu JJ, Chen JX, Rothman TP, Gershon MD, (1999) Inhibition of in vitro enteric neuronal development by endothelin-3: mediation by endothelin B receptors. Development 126: 1161-1173
140. Yamaguchi TP, Bradley A, McMahon AP, Jones S, (1999) A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development 126: 1211-1223
141. Yang Q, Bermingham NA, Finegold MJ, Zoghbi HY, (2001) Requirement of Math1 for secretory cell lineage commitment in the mouse intestine. Science 294: 2155-2158
142. Yang X, Dormann D, Münsterberg AE, Weijer CJ, (2002) Cell movement patterns during gastrulation in the chick are controlled by positive and negative chemotaxis mediated by FGF4 and FGF8. Dev Cell 3: 425-437
143. + stem cell. Nat Med 18: 618-623
144. Zecchini V, Domaschenz R, Winton D, Jones P, (2005) Notch signaling regulates the differentiation of post-mitotic intestinal epithelial cells. Genes Dev 19: 1686-1691
145. Zhang Z, Rankin SA, Zorn AM, (2013) Different thresholds of Wnt-Frizzled 7 signaling coordinate proliferation, morphogenesis and fate of endoderm progenitor cells. Dev Biol 378: 1-12
146. Zhu L, Lee H-O, Jordan CS, Cantrell VA, Southard-Smith EM, Shin MK, (2004) Spatiotemporal regulation of endothelin receptor-B by SOX10 in neural crest-derived enteric neuron precursors. Nat Genet 36: 732-737
147. Zorn AM, Butler K, Gurdon JB, (1999) Anterior endomesoderm specification in Xenopus by Wnt/beta-catenin and TGF-beta signalling pathways. Dev Biol 209: 282-297
148. Zorn AM, Wells JM, (2007) Molecular basis of vertebrate endoderm development. Int Rev Cytol 259: 49-111
149. Zorn AM, Wells JM, (2009) NIH Public Access. Annu Rev Cell Dev Biol 25: 221-251