Transcriptome-wide Analysis Reveals Hallmarks of Human Intestine Development and Maturation In Vitro and In Vivo
- Creators
- Finkbeiner, Stacy R.
- Hill, David R.
- Altheim, Christopher H.
- Dedhia, Priya H.
- Taylor, Matthew J.
- Tsai, Yu-Hwai
- Chin, Alana M.
- Mahe, Maxime M.
- Watson, Carey L.
- Freeman, Jennifer J.
- Nattiv, Roy
-
Thomson, Matthew
- Klein, Ophir D.
- Shroyer, Noah F.
- Helmrath, Michael A.
- Teitelbaum, Daniel H.
- Dempsey, Peter J.
- Spence, Jason R.
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.
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.Attached Files
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Additional details
- PMCID
- PMC4471827
- Eprint ID
- 74413
- Resolver ID
- CaltechAUTHORS:20170217-155108581
- NIH
- K01DK091415
- NIH
- U01DK103141
- NIH
- 5P30DK034933
- NIH Predoctoral Fellowship
- T32DK094775
- Hartwell Foundation
- NIH
- 2UL1TR000433
- California Institute for Regenerative Medicine (CIRM)
- RN3-06525
- Created
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2017-02-18Created from EPrint's datestamp field
- Updated
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2021-11-11Created from EPrint's last_modified field