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Extrusion of BMP2+ surface colonocytes promotes stromal remodeling and tissue regeneration

The mechanisms driving epithelial regeneration in the colon are not well understood. Here, the authors show that IFN-γ, produced by immune cells in response to chemically induced colitis, acts as a central driver of crypt reorganization by inducing apoptosis and extrusion of BMP2-expressing colonocytes.

Julian Heuberger
Lichao Liu
Michael Sigal
ResearchOpen Access03 May 2025
Nature Communications

Volume: 16, P: 1-17
Establishment of gastrointestinal assembloids to study the interplay between epithelial crypts and their mesenchymal niche

Most intestinal organoid models do not accurately model the interactions between epithelial and stromal cells. Here they establish a colon assembloid system with epithelial and stromal cells and demonstrate that BMP signals from differentiating epithelial cells promote mesenchymal niche organization.

Manqiang Lin
Kimberly Hartl
Michael Sigal
ResearchOpen Access25 May 2023
Nature Communications

Volume: 14, P: 1-14
R-spondin 3 promotes stem cell recovery and epithelial regeneration in the colon

Epithelial turnover in the colon requires stem cells in the crypt that express the R-spondin receptor Lgr5. Here, the authors show that regeneration after colon injury involving loss of Lgr5⁺ and Axin2⁺ cells requires stromal derived Rspo3-dependent reprogramming of Lgr4⁺ differentiated cells, including Krt20⁺ enterocytes.

Christine Harnack
Hilmar Berger
Michael Sigal
ResearchOpen Access25 Sept 2019
Nature Communications

Volume: 10, P: 1-15
Genomic aberrations after short-term exposure to colibactin-producing E. coli transform primary colon epithelial cells

Colibactin-producing pks+ Escherichia coli are frequent constituents of the human intestinal microbiota. Here, the authors show that short exposure of cells to pks+ E. coli induces chromosomal aberrations, genomic instability, and multiple features of transformation reminiscent of colorectal cancer.

Amina Iftekhar
Hilmar Berger
Thomas F. Meyer
ResearchOpen Access12 Feb 2021
Nature Communications

Volume: 12, P: 1-15
Modelling Chlamydia and HPV co-infection in patient-derived ectocervix organoids reveals distinct cellular reprogramming

Here, Koster et al., model human papillomavirus and Chlamydia coinfection dynamics in patient-derived ectocervical organoids, and characterize the effects of multiple infections in the cellular microenvironment, potentially contributing to neoplasia.

Stefanie Koster
Rajendra Kumar Gurumurthy
Cindrilla Chumduri
ResearchOpen Access24 Feb 2022
Nature Communications

Volume: 13, P: 1-15
Opposing Wnt signals regulate cervical squamocolumnar homeostasis and emergence of metaplasia

Chumduri, Gurumurthy et al. show that cervical squamous and columnar epithelia derive from two stem cell populations, regulated by opposing Wnt signals, and that a Wnt-repressive environment can induce metaplasia.

Cindrilla Chumduri
Rajendra Kumar Gurumurthy
Thomas F. Meyer
ResearchOpen Access18 Jan 2021
Nature Cell Biology

Volume: 23, P: 184-197
BMP feed-forward loop promotes terminal differentiation in gastric glands and is interrupted by H. pylori-driven inflammation

Helicobacter pylori causes gastric inflammation, gland hyperplasia and is linked to gastric cancer. Here the authors identify a BMP feedback loop between the stomach epithelium and surrounding stroma that controls gland homeostasis and demonstrate its interruption upon infection with H. pylori.

Marta Kapalczynska
Manqiang Lin
Michael Sigal
ResearchOpen Access24 Mar 2022
Nature Communications

Volume: 13, P: 1-18
Chronic Chlamydia infection in human organoids increases stemness and promotes age-dependent CpG methylation

Chronic infections of the fallopian tubes with Chlamydia trachomatis can cause scarring and infertility. Here, the authors show that the pathogen alters stem cell differentiation and DNA methylation in human fallopian tube organoids, suggesting a potential link to cellular ageing and malignant transformation.

Mirjana Kessler
Karen Hoffmann
Thomas F. Meyer
ResearchOpen Access18 Mar 2019
Nature Communications

Volume: 10, P: 1-14
R-spondin-3 induces secretory, antimicrobial Lgr5⁺ cells in the stomach

Sigal et al. report that Rspo3 regulates Lgr5 cells in the gastric gland base, induces their differentiation into secretory cells and stimulates epithelial antimicrobial defence against H. pylori infection.

Michael Sigal
Maria del Mar Reinés
Thomas F. Meyer
Research24 Jun 2019
Nature Cell Biology

Volume: 21, P: 812-823
The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids

The mechanisms underlying fallopian tube epithelial renewal are unclear. Here, Kessler et al. isolate adult stem cells from the human fallopian tube epithelium and generate 3D organoids from these cells in vitrothat have a similar architecture to that of the fallopian tube.

Mirjana Kessler
Karen Hoffmann
Thomas F. Meyer
ResearchOpen Access08 Dec 2015
Nature Communications

Volume: 6, P: 1-11
Colibactin DNA-damage signature indicates mutational impact in colorectal cancer

Identification of a DNA-damage signature induced by colibactin, a toxin expressed by some strains of Escherichia coli, is enriched in human colorectal cancers.

Paulina J. Dziubańska-Kusibab
Hilmar Berger
Thomas F. Meyer
Research01 Jun 2020
Nature Medicine

Volume: 26, P: 1063-1069
Stromal R-spondin orchestrates gastric epithelial stem cells and gland homeostasis

Myofibroblast-derived R-spondin 3 orchestrates regeneration of antral stomach epithelium via Wnt signalling in Axin2⁺ stem cells.

Michael Sigal
Catriona Y. Logan
Thomas F. Meyer
Research16 Aug 2017
Nature

Volume: 548, P: 451-455
Expression of Cyclin E1 in hepatic stellate cells is critical for the induction and progression of liver fibrosis and hepatocellular carcinoma in mice

Julia Otto
Anna Verwaayen
Christian Liedtke
ResearchOpen Access24 Aug 2023
Cell Death & Disease

Volume: 14, P: 1-15

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Extrusion of BMP2+ surface colonocytes promotes stromal remodeling and tissue regeneration

Establishment of gastrointestinal assembloids to study the interplay between epithelial crypts and their mesenchymal niche

R-spondin 3 promotes stem cell recovery and epithelial regeneration in the colon

Genomic aberrations after short-term exposure to colibactin-producing E. coli transform primary colon epithelial cells

Modelling Chlamydia and HPV co-infection in patient-derived ectocervix organoids reveals distinct cellular reprogramming

Opposing Wnt signals regulate cervical squamocolumnar homeostasis and emergence of metaplasia

BMP feed-forward loop promotes terminal differentiation in gastric glands and is interrupted by H. pylori-driven inflammation

Chronic Chlamydia infection in human organoids increases stemness and promotes age-dependent CpG methylation

R-spondin-3 induces secretory, antimicrobial Lgr5⁺ cells in the stomach

The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids

Colibactin DNA-damage signature indicates mutational impact in colorectal cancer

Stromal R-spondin orchestrates gastric epithelial stem cells and gland homeostasis

Expression of Cyclin E1 in hepatic stellate cells is critical for the induction and progression of liver fibrosis and hepatocellular carcinoma in mice

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