Growing Self-Organizing Mini-Guts from a Single Intestinal Stem Cell: Mechanism and Applications
Abstract
Recent examples have highlighted how stem cells have the capability to initiate morphogenesis in vitro; that is, to generate complex structures in culture that closely parallel their in vivo counterparts. Lgr5, the receptor for the Wnt-agonistic R-spondins, marks stem cells in multiple adult organs of mice and humans. In R-spondin–based three-dimensional cultures, these Lgr5 stem cells can grow into ever-expanding epithelial organoids that retain their original organ identity. Single Lgr5 stem cells derived from the intestine can be cultured to build epithelial structures that retain hallmarks of the in vivo epithelium. Here, we review the mechanisms that support this notable example of self-organization and discuss applications of this technology for stem cell research, disease modeling (e.g., for colorectal cancer and cystic fibrosis), and regenerative medicine.
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Matrigel has been successfully utilized in several epithelial stem cell platforms.
“Next, we examined whether embedding cells in a basement membrane-like extracellular 3D environment such as Matrigel, which has been successfully utilized in several epithelial stem cell platforms, could enable establishment of SG organoids (Fig. 1d)12–14.”
From Blimp1+ cells generate functional mouse sebaceous gland organoids in vitro (2019) · cites this paper as [12]
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- Authors
- Sato, T., & Clevers, H.
- Affiliations
- Keio University (JP)
- Royal Netherlands Academy of Arts and Sciences (NL)
- Corresponding author
- Sato, Toshiro
- Clevers, Hans
- Venue
- Science
- Published
- 2013-06-07
- Volume
- 340
- Issue
- 6137
- Pages
- 1190-1194
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1997114875
- Cited by
- 1,170
- References
- 8
- Citations by year
- 2026: 44 · 2025: 64 · 2024: 89 · 2023: 74 · 2022: 104 · 2021: 116 · 2020: 96 · 2019: 106 · 2018: 97 · 2017: 81 · 2016: 110 · 2015: 82 · 2014: 84 · 2013: 21 · 2012: 1
- FWCI
- 9.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (24689036)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- intestinal stem cells, Lgr5, R-spondin, Wnt signaling, organoid formation, self-organization, 3D cell culture, regenerative medicine, organogenesis
- MeSH terms
- Animals, Cell Count, Disease Models, Animal, Humans, Intestinal Mucosa, Intestine, Small, Morphogenesis, Cell Culture Techniques, Ephrin-B1, Receptors, G-Protein-Coupled, Regenerative Medicine, Wnt Proteins, Mice, Adult Stem Cells, Stem Cell Niche
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