@article{db6a916a25aa4649b6cd628c4f6b423c,
title = "Enteroid Monolayers Reveal an Autonomous WNT and BMP Circuit Controlling Intestinal Epithelial Growth and Organization",
abstract = "The intestinal epithelium maintains a remarkable balance between proliferation and differentiation despite rapid cellular turnover. A central challenge is to elucidate mechanisms required for robust control of tissue renewal. Opposing WNT and BMP signaling is essential in establishing epithelial homeostasis. However, it has been difficult to disentangle contributions from multiple sources of morphogen signals in the tissue. Here, to dissect epithelial-autonomous morphogenic signaling circuits, we developed an enteroid monolayer culture system that recapitulates four key properties of the intestinal epithelium, namely the ability to maintain proliferative and differentiated zones, self-renew, polarize, and generate major intestinal cell types. We systematically perturb intrinsic and extrinsic sources of WNT and BMP signals to reveal a core morphogenic circuit that controls proliferation, tissue organization, and cell fate. Our work demonstrates the ability of intestinal epithelium, even in the absence of 3D tissue architecture, to control its own growth and organization through morphogen-mediated feedback. Thorne, Chen et al. develop an enteroid monolayer culture system that recapitulates cell-type composition, crypt organization, and turnover kinetics of the intestinal epithelium. The authors use the enteroid monolayer to uncover an epithelium-intrinsic Wnt and BMP morphogenic circuit that regulates proliferation and tissue organization in the intestinal epithelium.",
keywords = "BMP, Wnt, crypt, epithelium, feedback, homeostasis, intestine, organoid, proliferation",
author = "Thorne, {Curtis A.} and Chen, {Ina W.} and Sanman, {Laura E.} and Cobb, {Melanie H.} and Wu, {Lani F.} and Altschuler, {Steven J.}",
note = "Funding Information: We are grateful to Sigurd B. Angenent, James J. Collins II, and Chonlarat Wichaidit for their insightful feedback. We thank David Manglesdorf, Ophir Klein, Frederic de Sauvage, and Genaro Hernandez for mouse resources and Andres Lorente-Rodriguez for the custom ImageJ macro. We also thank the anonymous reviewers for their helpful input. This work was supported by a Cancer Biology Training grant T32 CA124334 (C.A.T.), an American Cancer Society–Lakeshore Division Postdoctoral Fellowship (C.A.T.), the NIH grant R00 DK103126 (C.A.T.), a National Science Foundation Graduate Research Fellowship (I.W.C), R37 DK34128 (M.H.C.), Welch I1243 (M.H.C.), GM112690 (S.J.A.), and R01CA184984 (L.F.W.), and the Institute of Computational Health Sciences (ICHS) at UCSF (S.J.A. and L.F.W.). Funding Information: We are grateful to Sigurd B. Angenent, James J. Collins II, and Chonlarat Wichaidit for their insightful feedback. We thank David Manglesdorf, Ophir Klein, Frederic de Sauvage, and Genaro Hernandez for mouse resources and Andres Lorente-Rodriguez for the custom ImageJ macro. We also thank the anonymous reviewers for their helpful input. This work was supported by a Cancer Biology Training grant T32 CA124334 (C.A.T.), an American Cancer Society–Lakeshore Division Postdoctoral Fellowship (C.A.T.), the NIH grant R00 DK103126 (C.A.T.), a National Science Foundation Graduate Research Fellowship (I.W.C), R37 DK34128 (M.H.C.), Welch I1243 (M.H.C.), GM112690 (S.J.A.), and R01CA184984 (L.F.W.), and the Institute of Computational Health Sciences (ICHS) at UCSF (S.J.A. and L.F.W.). Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2018",
month = mar,
day = "12",
doi = "10.1016/j.devcel.2018.01.024",
language = "English (US)",
volume = "44",
pages = "624--633.e4",
journal = "Developmental cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "5",
}