Controlled gene expression in primary Lgr5 organoid cultures
Abstract
The study of gene function in endodermal epithelia such as of stomach, small intestine and colon relies heavily on transgenic approaches. Establishing such animal models is laborious, expensive and time-consuming. We present here a method based on Cre recombinase-inducible retrovirus vectors that allows the conditional manipulation of gene expression in primary mouse organoid culture systems.
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Viral vectors provide the highest transfection efficiency but have serious limitations such as the size of DNA carried, intrinsic biosafety issues, concern for viral insertion mutagenesis, and an inability to diffuse through ECM.
“Viral vectors provide the highest transfection efficiency but have serious limitations such as the size of DNA carried in the vector, intrinsic biosafety issues, concern for viral insertion mutagenesis (11) and an inability to diffuse through ECM (12).”
From Direct transfection of clonal organoids in Matrigel microbeads: a promising approach toward organoid-based genetic screens (2018) · cites this paper as [12]
ECM impedes virus-mediated gene delivery since its digestion dramatically improves extinction efficiency.
“While viral transduction systems usually allow higher transfection efficiencies, it has been demonstrated that ECM impedes virus-mediated gene delivery since its digestion dramatically improves extinction efficiency (12), which explains the limited effect on Matrigel microbeads.”
From Direct transfection of clonal organoids in Matrigel microbeads: a promising approach toward organoid-based genetic screens (2018) · cites this paper as [12]
Retroviral infection allowed sustained expression of GFP in more than 90% of cells from organoid fragments removed from Matrigel.
“For example, retroviral infection allowed the sustained expression of GFP in more than 90% of cells from organoid fragments that were removed from Matrigel (12).”
From Direct transfection of clonal organoids in Matrigel microbeads: a promising approach toward organoid-based genetic screens (2018) · cites this paper as [12]
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- Authors
- Koo, B.-K., Stange, D. E., Sato, T., Karthaus, W., Farin, H. F., Huch, M., van Es, J. H., & Clevers, H.
- Affiliations
- University Medical Center Utrecht (NL)
- Keio University (JP)
- Corresponding author
- Clevers, Hans
- ORCID
- Venue
- Nature Methods
- Published
- 2011-12-04
- Volume
- 9
- Issue
- 1
- Pages
- 81-83
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- OpenAlex
- W2110537190
- Cited by
- 320
- References
- 14
- Citations by year
- 2026: 11 · 2025: 19 · 2024: 13 · 2023: 22 · 2022: 17 · 2021: 25 · 2020: 25 · 2019: 27 · 2018: 27 · 2017: 24 · 2016: 30 · 2015: 26 · 2014: 23 · 2013: 20 · 2012: 11
- FWCI
- 10.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Methods (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
- Wellcome Trust (104151)
- Japan Society for the Promotion of Science (23890204)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
- Keywords
- Lgr5, organoids, gene overexpression, gene knockdown, Cre recombinase, retroviral vectors, mice
- MeSH terms
- Animals, Humans, Intestinal Mucosa, Organoids, Retroviridae, Stem Cells, Tamoxifen, Transduction, Genetic, Gene Expression, Integrases, Receptors, G-Protein-Coupled, Green Fluorescent Proteins, Mice, Receptors, Notch, Gene Knockdown Techniques
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