The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Terminal differentiation of villus-tip enterocytes is governed by distinct members of Tgfβ superfamily
Open accessPreprint — published as 10.15252/embr.202256454
Abstract
The protective and absorptive functions of the intestinal epithelium rely on differentiated enterocytes in the villi. The differentiation of enterocytes is orchestrated by sub-epithelial mesenchymal cells producing distinct ligands along the villus axis, in particular Bmps and Tgfβ. Here we show that individual Bmp ligands and Tgfβ drive distinct enterocytic programs specific to villus zonation. Bmp4 is expressed mainly from the center to the upper part of the villus, and it activates preferentially genes connected to lipid uptake and metabolism. In contrast, Bmp2 is produced by villus-tip mesenchymal cells, and it influences the adhesive properties of villus-tip epithelial cells and the expression of immunomodulators. Hence, Bmp2 promotes the terminal enterocytic differentiation at the villus-tip. Additionally, Tgfβ induces epithelial gene expression programs similar to that triggered by Bmp2. The inhibition of Bmp receptor type I in vivo and using intestinal organoids lacking Smad4 revealed that Bmp2-driven villus-tip program is activated by a canonical Smad-dependent mechanism. Finally, we established an organoid cultivation system that enriches for villus-tip enterocytes and thereby better mimics the cellular composition of the intestinal epithelium. Altogether our data suggest that not only Bmp gradient, but also the activity of individual Bmp drives specific enterocytic programs.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566
Flagged first, then by citations
Research works printed but not linked: 35
- 10.1098/rsob.180120 · DOI
- 10.1038/s41575-018-0081-y · DOI
- 2021, Spatial discordances between mRNAs and proteins in the intestinal epithelium, Nat Metab, 3, 1680, 10.1038/s42255-021-00504-6 · DOI
- 10.1016/j.cell.2018.08.063 · DOI · Paper page
- 10.1073/pnas.1713510115 · DOI · Paper page
- 10.1016/j.stem.2020.01.008 · DOI
- 10.1371/journal.pbio.3001032 · DOI
- 10.1038/s41586-018-0190-3 · DOI
- 2014, Bone Morphogenetic Protein (BMP) signaling in development and human diseases, Genes & Diseases, 1, 87, 10.1016/j.gendis.2014.07.005 · DOI
- 10.1038/nrendo.2016.12 · DOI · Paper page
- 10.1038/ncomms13824 · DOI · Paper page
- 2022, BMP gradient along the intestinal villus axis controls zonated enterocyte and goblet cell states, Cell Reports, 38, 110438, 10.1016/j.celrep.2022.110438 · DOI
- 2022, Intestinal epithelial c-Maf expression determines enterocyte differentiation and nutrient uptake in mice, Journal of Experimental Medicine, 219, e20220233, 10.1084/jem.20220233 · DOI
- 2022, c-MAF coordinates enterocyte zonation and nutrient uptake transcriptional programs, Journal of Experimental Medicine, 219, e20212418, 10.1084/jem.20212418 · DOI
- 10.1038/s41467-020-15714-x · DOI
- 10.1016/j.cellsig.2010.10.003 · DOI · Paper page
- 10.48550/ARXIV.2110.08209 · DOI
- 10.1038/nature24489 · DOI · Paper page
- 10.1101/2020.01.22.914689 · DOI
- 10.1038/nature14966 · DOI · Paper page
- 10.1016/j.stem.2018.11.016 · DOI · Paper page
- 10.1126/science.1093587 · DOI
- 2017, Transforming growth factor β: a master regulator of the gut microbiota and immune cell interactions, Clin Trans Immunol, 6, e136, 10.1038/cti.2017.9 · DOI
- 2020, Role of TGF-Beta and Smad7 in Gut Inflammation, Fibrosis and Cancer, Biomolecules, 11, 17, 10.3390/biom11010017 · DOI
- 10.1016/S0002-9440(10)61243-6 · DOI
- 10.1126/science.1223821 · DOI
- 10.1128/MCB.23.11.4013-4025.2003 · DOI
- 10.1038/nature07935 · DOI · Paper page
- 10.1038/nature09637 · DOI · Paper page
- 2021, Cell fate coordinates mechano-osmotic forces in intestinal crypt formation, Nat Cell Biol, 23, 733, 10.1038/s41556-021-00700-2 · DOI · Paper page
- 2012, Somatic Stem Cells, 879, 89, 10.1007/978-1-61779-815-3_6 · DOI
- 10.1038/s41587-020-0439-x · DOI
- 10.1038/nmeth.4197 · DOI · Paper page
- 10.1093/NAR/GKAA942 · DOI
- 10.1186/s13059-014-0550-8 · DOI · Paper page
Metadata
- Authors
- Berková, L., Fazilaty, H., Yang, Q., Kubovčiak, J., Stastna, M., Hrckulak, D., Vojtechova, M., Brügger, M. D., Hausmann, G., Liberali, P., Korinek, V., Basler, K., & Valenta, T.
- Affiliations
- Czech Academy of Sciences (CZ)
- University of Zurich (CH)
- Chinese Academy of Sciences (CN)
- Friedrich Miescher Institute (CH)
- Corresponding author
- Basler, Konrad
- ORCID
- Venue
- EMBO Reports
- Publisher
- openRxiv
- Published
- 2022-11-12
- Volume
- 24
- Issue
- 9
- Pages
- e56454-e56454
- ISSN
- 1469-221X (ISSN-L)
- PMC
- PMC10481656
- OpenAlex
- W4385263797
- Cited by
- 28
- References
- 1
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 13 · 2023: 2
- FWCI
- 2.50
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- EMBO Reports (publishedVersion, other-oa)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Science Foundation
- European Commission (LX22NPO5102)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Grantová Agentura České Republiky (GA21-26025S)
- NextGenerationEU
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Gastroenterology › Digestive system and related health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- enterocyte differentiation, BMP signaling, TGF-beta superfamily, BMP4, BMP-2, Smad signaling, intestinal epithelium, lipid uptake, immunomodulators, epithelial cell adhesion, intestinal organoids, epithelial-mesenchymal interactions
- MeSH terms
- Cell Differentiation, Intestinal Mucosa, Ligands, Transforming Growth Factor beta, Bone Morphogenetic Proteins, Enterocytes
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
