Cited by 196Cancer Cells and MetastasisWnt/β-catenin signaling in development and cancerPluripotent Stem Cells Research

Reconstruction of the Human Colon Epithelium In Vivo

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Sugimoto, Shinya, Ohta, Yuki, Fujii, Masayuki, Matano, Mami, Shimokawa, Mariko, Nanki, Kosaku, Date, Shoichi, Nishikori, Shingo +4 more·2018·Cell Stem Cell

Abstract

Genetic lineage tracing has revealed that Lgr5 + murine colon stem cells (CoSCs) rapidly proliferate at the crypt bottom. However, the spatiotemporal dynamics of human CoSCs in vivo have remained experimentally intractable. Here we established an orthotopic xenograft system for normal human colon organoids, enabling stable reconstruction of the human colon epithelium in vivo. Xenografted organoids were prone to displacement by the remaining murine crypts, and this could be overcome by complete removal of the mouse epithelium. Xenografted organoids formed crypt structures distinctively different from surrounding mouse crypts, reflecting their human origin. Lineage tracing using CRISPR-Cas9 to engineer an LGR5-CreER knockin allele demonstrated self-renewal and multipotency of LGR5 + CoSCs. In contrast to the rapidly cycling properties of mouse Lgr5 + CoSCs, human LGR5 + CoSCs were slow-cycling in vivo. This organoid-based orthotopic xenograft model enables investigation of the functional behaviors of human CoSCs in vivo, with potential therapeutic applications in regenerative medicine.

Integrity signals

Registry

Crossref · 10.1016/j.stem.2017.11.012

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32 of 32 references verified0 citation errors · 0 not checkable

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  • The formation of organoids recapitulates a 3D in vivo-like microenvironment that may compensate for the lack of structural support for tissue formation in the damaged extracellular matrix environment when used as xenografts.

    “the formation of organoids also recapitulate a 3D in vivo‐like microenvironment that may well compensate for the lack of structural support for tissue formation in the damaged extracellular matrix environment when used as xenografts.[ 18 , 19 ]”

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Authors
Sugimoto, S., Ohta, Y., Fujii, M., Matano, M., Shimokawa, M., Nanki, K., Date, S., Nishikori, S., Nakazato, Y., Nakamura, T., Kanai, T., & Sato, T.
Affiliations
  • Keio University (JP)
  • Otsuka (Japan) (JP)
  • Tokyo Medical and Dental University (JP)
Corresponding author
Sato, Toshiro
Venue
Cell Stem Cell
Publisher
Elsevier BV
Published
2018-02
Volume
22
Issue
2
Pages
171-176.e5
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
OpenAlex
W2780908039
Cited by
196
References
32
Citations by year
2026: 9 · 2025: 24 · 2024: 24 · 2023: 18 · 2022: 28 · 2021: 34 · 2020: 30 · 2019: 17 · 2018: 11 · 2017: 1
FWCI
7.16
Type
journal article
Language
en
Open access
Locations
  • Cell stem cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Japan Agency for Medical Research and Development
  • Japan Society for the Promotion of Science (JP26115007, JP15J00981)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Keywords
Lgr5, orthotopic xenograft, colon organoids, regenerative medicine
MeSH terms
Animals, Colon, Humans, Intestinal Mucosa, Male, Organoids, Regeneration, Transplantation, Heterologous, Receptors, G-Protein-Coupled, Mice

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