Screening for modulators of the cellular composition of gut epithelia via organoid models of intestinal stem cell differentiation Article Swipe
Benjamin E. Mead
,
Kazuki Hattori
,
Lauren Levy
,
Shinya Imada
,
Norihiro Goto
,
Marko Vukovic
,
Daphne Sze
,
Conner Kummerlowe
,
Juan D. Matute
,
Jinzhi Duan
,
Róbert Langer
,
Richard S. Blumberg
,
José Ordovás-Montañés
,
Ömer Yılmaz
,
Jeffrey M. Karp
,
Alex K. Shalek
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1038/s41551-022-00863-9
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1038/s41551-022-00863-9
The cellular composition of barrier epithelia is essential to organismal homoeostasis. In particular, within the small intestine, adult stem cells establish tissue cellularity, and may provide a means to control the abundance and quality of specialized epithelial cells. Yet, methods for the identification of biological targets regulating epithelial composition and function, and of small molecules modulating them, are lacking. Here we show that druggable biological targets and small-molecule regulators of intestinal stem cell differentiation can be identified via multiplexed phenotypic screening using thousands of miniaturized organoid models of intestinal stem cell differentiation into Paneth cells, and validated via longitudinal single-cell RNA-sequencing. We found that inhibitors of the nuclear exporter Exportin 1 modulate the fate of intestinal stem cells, independently of known differentiation cues, significantly increasing the abundance of Paneth cells in the organoids and in wild-type mice. Physiological organoid models of the differentiation of intestinal stem cells could find broader utility for the screening of biological targets and small molecules that can modulate the composition and function of other barrier epithelia.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s41551-022-00863-9
- https://www.nature.com/articles/s41551-022-00863-9.pdf
- OA Status
- hybrid
- Cited By
- 50
- References
- 72
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4221112718
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4221112718Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1038/s41551-022-00863-9Digital Object Identifier
- Title
-
Screening for modulators of the cellular composition of gut epithelia via organoid models of intestinal stem cell differentiationWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-03-21Full publication date if available
- Authors
-
Benjamin E. Mead, Kazuki Hattori, Lauren Levy, Shinya Imada, Norihiro Goto, Marko Vukovic, Daphne Sze, Conner Kummerlowe, Juan D. Matute, Jinzhi Duan, Róbert Langer, Richard S. Blumberg, José Ordovás-Montañés, Ömer Yılmaz, Jeffrey M. Karp, Alex K. ShalekList of authors in order
- Landing page
-
https://doi.org/10.1038/s41551-022-00863-9Publisher landing page
- PDF URL
-
https://www.nature.com/articles/s41551-022-00863-9.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
-
https://www.nature.com/articles/s41551-022-00863-9.pdfDirect OA link when available
- Concepts
-
Organoid, Stem cell, Cell biology, Biology, Cellular differentiation, Intestinal epithelium, Paneth cell, Small intestine, Cell type, Cell, Intestinal mucosa, Epithelium, Biochemistry, Genetics, Gene, Internal medicine, MedicineTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
50Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 8, 2024: 21, 2023: 14, 2022: 7Per-year citation counts (last 5 years)
- References (count)
-
72Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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