191McGrath PS, Watson CL, Ingram C, Helmrath MA, Wells JM (2015) The basic Helix-Loop-Helix
transcription factor NEUROG3 is required for development of the human endocrine pancreas.
Diabetes 64:2497–2505
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 (Cambridge, England)
134:2207–2217
Montgomery RK, Mulberg AE, Grand RJ (1999) Development of the human gastrointestinal tract:
twenty years of progress. Gastroenterology 116:702–731
Mustata RC, Vasile G, Fernandez-Vallone V, Strollo S, Lefort A, Libert F, Monteyne D, Perez-
Morga D, Vassart G, Garcia MI (2013) Identification of Lgr5-independent spheroid-generating
progenitors of the mouse fetal intestinal epithelium. Cell Rep 5:421–432
Niederreither K, Vermot J, Le Roux I, Schuhbaur B, Chambon P, Dolle 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 (Cambridge, England) 130:2525–2534
Quinlan JM, Colleypriest BJ, Farrant M, Tosh D (2007) Epithelial metaplasia and the development
of cancer. Biochim Biophys Acta 1776:10–21
Ramalho-Santos M, Melton DA, McMahon AP (2000) Hedgehog signals regulate multiple aspects
of gastrointestinal development. Development 127:2763–2772
Rankin SA, Kormish J, Kofron M, Jegga A, Zorn AM (2011) A gene regulatory network control-
ling hhex transcription in the anterior endoderm of the organizer. Dev Biol 351:297–310
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
Rothenberg ME, Nusse Y, Kalisky T, Lee JJ, Dalerba P, Scheeren F, Lobo N, Kulkarni S, Sim S,
Qian D et al (2012) Identification of a cKit(+) colonic crypt base secretory cell that supports
Lgr5(+) stem cells in mice. Gastroenterology 142(1195–1205):e1196
San Roman AK, Shivdasani RA (2011) Boundaries, junctions and transitions in the gastrointesti-
nal tract. Exp Cell Res 317:2711–2718
Sasaki N, Sachs N, Wiebrands K, Ellenbroek SIJ, Fumagalli A, Lyubimova A, Begthel H, van den
Born M, van Es JH, Karthaus WR et al (2016) Reg4+ deep crypt secretory cells function as
epithelial niche for Lgr5+ stem cells in colon. Proc Natl Acad Sci U S A 113:E5399–E5407
Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala
P, Peters PJ et al (2009) Single Lgr5 stem cells build crypt-villus structures in vitro without a
mesenchymal niche. Nature 459:262–265
Sato T, Stange DE, Ferrante M, Vries RG, Van Es JH, Van den Brink S, Van Houdt WJ, Pronk A, Van
Gorp J, Siersema PD et al (2011a) Long-term expansion of epithelial organoids from human
colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology 141:1762–1772
Sato T, van Es JH, Snippert HJ, Stange DE, Vries RG, van den Born M, Barker N, Shroyer NF, van
de Wetering M, Clevers H (2011b) Paneth cells constitute the niche for Lgr5 stem cells in
intestinal crypts. Nature 469:415–418
Sherwood RI, Chen T-YA, Melton DA (2009a) Transcriptional dynamics of endodermal organ
formation. Dev Dyn 238:29–42
Sherwood RI, Chen TY, Melton DA (2009b) Transcriptional dynamics of endodermal organ for-
mation. Dev Dyn Off Publ Am Assoc Anat 238:29–42
Sherwood RI, Maehr R, Mazzoni EO, Melton DA (2011) Wnt signaling specifies and patterns
intestinal endoderm. Mech Dev 128:387–400
Shyer AE, Huycke TR, Lee C, Mahadevan L, Tabin CJ (2015) Bending gradients: how the intesti-
nal stem cell gets its home. Cell 161:569–580
Snippert HJ, van der Flier LG, Sato T, van Es JH, van den Born M, Kroon-Veenboer C, Barker N,
Klein AM, van Rheenen J, Simons BD et al (2010) Intestinal crypt homeostasis results from
neutral competition between symmetrically dividing Lgr5 stem cells. Cell 143:134–144
Soucy G, Wang HH, Farraye FA, Schmidt JF, Farris AB, Lauwers GY, Cerda SR, Dendrinos KG,
Odze RD (2012) Clinical and pathological analysis of colonic Crohn’s disease, including a
subgroup with ulcerative colitis-like features. Mod Pathol 25:295–307
10 Generation of Gastrointestinal Organoids Derived from Human Pluripotent Stem...