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Transcriptome-wide Analysis Reveals Hallmarks of Human Intestine Development and Maturation In Vitro and In Vivo

Finkbeiner, Stacy R. and Hill, David R. and Altheim, Christopher H. and Dedhia, Priya H. and Taylor, Matthew J. and Tsai, Yu-Hwai and Chin, Alana M. and Mahe, Maxime M. and Watson, Carey L. and Freeman, Jennifer J. and Nattiv, Roy and Thomson, Matthew and Klein, Ophir D. and Shroyer, Noah F. and Helmrath, Michael A. and Teitelbaum, Daniel H. and Dempsey, Peter J. and Spence, Jason R. (2015) Transcriptome-wide Analysis Reveals Hallmarks of Human Intestine Development and Maturation In Vitro and In Vivo. Stem Cell Reports, 4 (6). pp. 1140-1155. ISSN 2213-6711. PMCID PMC4471827. https://resolver.caltech.edu/CaltechAUTHORS:20170217-155108581

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Abstract

Human intestinal organoids (HIOs) are a tissue culture model in which small intestine-like tissue is generated from pluripotent stem cells. By carrying out unsupervised hierarchical clustering of RNA-sequencing data, we demonstrate that HIOs most closely resemble human fetal intestine.We observed that genes involved in digestive tract development are enriched in both fetal intestine and HIOs compared to adult tissue, whereas genes related to digestive function and Paneth cell host defense are expressed at higher levels in adult intestine. Our study also revealed that the intestinal stem cell marker OLFM4 is expressed at very low levels in fetal intestine and in HIOs, but is robust in adult crypts.We validated our findings using in vivo transplantation to show that HIOs become more adult-like after transplantation. Our study emphasizes important maturation events that occur in the intestine during human development and demonstrates that HIOs can be used to model fetal-to-adult maturation.


Item Type:Article
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https://dx.doi.org/10.1016/j.stemcr.2015.04.010DOIArticle
http://www.sciencedirect.com/science/article/pii/S2213671115001228PublisherArticle
http://www.cell.com/cms/attachment/2032431443/2048988833/mmc1.pdfPublisherSupplemental Information
http://www.cell.com/cms/attachment/2032431443/2048988819/mmc2.xlsxPublisherSupplemental Information
http://www.cell.com/cms/attachment/2032431443/2048988818/mmc3.xlsxPublisherSupplemental Information
http://www.cell.com/cms/attachment/2032431443/2048988820/mmc4.xlsxPublisherSupplemental Information
http://www.cell.com/cms/attachment/2032431443/2048988816/mmc5.xlsxPublisherSupplemental Information
http://www.cell.com/cms/attachment/2032431443/2048988817/mmc6.xlsxPublisherSupplemental Information
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471827/PubMed CentralArticle
Additional Information:© 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Received: December 16, 2014. Revised: April 22, 2015. Accepted: April 22, 2015. Published: June 4, 2015. We thank Rich McEachin and Manjusha Pande at the University of Michigan Bioinformatics Core Facility. We also thank the Gift of Life, Michigan, for access to human intestinal tissue. This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK, K01DK091415 and U01DK103141) to J.R.S. and by the University of Michigan Center for Gastrointestinal Research (UMCGR) (NIDDK, 5P30DK034933). Research reported in this publication and conducted by S.R.F. was supported by an NIDDK training grant, ‘‘Training in Basic and Translational Digestive Sciences’’ (T32DK094775), a postdoctoral fellowship from The Hartwell Foundation, and the National Center for Advancing Translational Sciences of the NIH (2UL1TR000433). Additionally, this work was supported by a grant from the California Institute for Regenerative Medicine (RN3-06525) to O.D.K. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Funders:
Funding AgencyGrant Number
NIHK01DK091415
NIHU01DK103141
NIH5P30DK034933
NIH Predoctoral FellowshipT32DK094775
Hartwell FoundationUNSPECIFIED
NIH2UL1TR000433
California Institute for Regenerative Medicine (CIRM)RN3-06525
Issue or Number:6
PubMed Central ID:PMC4471827
Record Number:CaltechAUTHORS:20170217-155108581
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170217-155108581
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74413
Collection:CaltechAUTHORS
Deposited By: Donna Wrublewski
Deposited On:18 Feb 2017 03:46
Last Modified:03 Oct 2019 16:38

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