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

Animals Epithelial Cells / metabolism Gastric Mucosa / metabolism Helicobacter Infections / metabolism Helicobacter pylori Inflammation / metabolism Ligands Mice

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
24 03 2022
Historique:
received: 21 09 2021
accepted: 19 02 2022
entrez: 25 3 2022
pubmed: 26 3 2022
medline: 13 4 2022
Statut: epublish

Résumé

Helicobacter pylori causes gastric inflammation, gland hyperplasia and is linked to gastric cancer. Here, we studied the interplay between gastric epithelial stem cells and their stromal niche under homeostasis and upon H. pylori infection. We find that gastric epithelial stem cell differentiation is orchestrated by subsets of stromal cells that either produce BMP inhibitors in the gland base, or BMP ligands at the surface. Exposure to BMP ligands promotes a feed-forward loop by inducing Bmp2 expression in the epithelial cells themselves, enforcing rapid lineage commitment to terminally differentiated mucous pit cells. H. pylori leads to a loss of stromal and epithelial Bmp2 expression and increases expression of BMP inhibitors, promoting self-renewal of stem cells and accumulation of gland base cells, which we mechanistically link to IFN-γ signaling. Mice that lack IFN-γ signaling show no alterations of BMP gradient upon infection, while exposure to IFN-γ resembles H. pylori-driven mucosal responses.

Identifiants

DOI: 10.1038/s41467-022-29176-w PMID: 35332152 PMC: PMC8948225
pubmed: 35332152
doi: 10.1038/s41467-022-29176-w
pii: 10.1038/s41467-022-29176-w
pmc: PMC8948225
doi:

Substances chimiques

Ligands 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1577

Informations de copyright

© 2022. The Author(s).

Références

Barker, N. et al. Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell 6, 25–36 (2010).
pubmed: 20085740 doi: 10.1016/j.stem.2009.11.013
Matsuo, J. et al. Identification of stem cells in the epithelium of the stomach corpus and antrum of mice. Gastroenterology 152, 218–231 e214 (2017).
pubmed: 27670082 doi: 10.1053/j.gastro.2016.09.018
Barker, N. et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449, 1003–1007 (2007).
pubmed: 17934449 doi: 10.1038/nature06196
Sigal, M. et al. Stromal R-spondin orchestrates gastric epithelial stem cells and gland homeostasis. Nature 548, 451–455 (2017).
pubmed: 28813421 doi: 10.1038/nature23642
Sigal, M. et al. Helicobacter pylori activates and expands Lgr5(+) stem cells through direct colonization of the gastric glands. Gastroenterology 148, 1392–1404 e1321 (2015).
pubmed: 25725293 doi: 10.1053/j.gastro.2015.02.049
Kim, H. S., Lee, C., Kim, W. H., Maeng, Y. H. & Jang, B. G. Expression profile of intestinal stem cell markers in colitis-associated carcinogenesis. Sci. Rep. 7, 6533 (2017).
pubmed: 28747693 pmcid: 5529509 doi: 10.1038/s41598-017-06900-x
Aihara, E. et al. Epithelial regeneration after gastric ulceration causes prolonged cell-type alterations. Cell Mol. Gastroenterol. Hepatol. 2, 625–647 (2016).
pubmed: 27766298 pmcid: 5042868 doi: 10.1016/j.jcmgh.2016.05.005
Sigal, M. et al. R-spondin-3 induces secretory, antimicrobial Lgr5(+) cells in the stomach. Nat. Cell Biol. 21, 812–823 (2019).
pubmed: 31235935 doi: 10.1038/s41556-019-0339-9
He, X. C. et al. BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling. Nat. Genet. 36, 1117–1121 (2004).
pubmed: 15378062 doi: 10.1038/ng1430
Kim, J. E. et al. Single cell and genetic analyses reveal conserved populations and signaling mechanisms of gastrointestinal stromal niches. Nat. Commun. 11, 334 (2020).
pubmed: 31953387 pmcid: 6969052 doi: 10.1038/s41467-019-14058-5
McCarthy, N. et al. Distinct mesenchymal cell populations generate the essential intestinal BMP signaling gradient. Cell Stem Cell 26, 391–402 e395 (2020).
pubmed: 32084389 pmcid: 7412576 doi: 10.1016/j.stem.2020.01.008
Van Zanten, S. J., Dixon, M. F. & Lee, A. The gastric transitional zones: neglected links between gastroduodenal pathology and helicobacter ecology. Gastroenterology 116, 1217–1229 (1999).
pubmed: 10220514 doi: 10.1016/S0016-5085(99)70025-9
Boccellato, F. et al. Polarised epithelial monolayers of the gastric mucosa reveal insights into mucosal homeostasis and defence against infection. Gut https://doi.org/10.1136/gutjnl-2017-314540 (2018).
Arnold, I. C. et al. Tolerance rather than immunity protects from Helicobacter pylori-induced gastric preneoplasia. Gastroenterology 140, 199–209 (2011).
pubmed: 20600031 doi: 10.1053/j.gastro.2010.06.047
Bamford, K. B. et al. Lymphocytes in the human gastric mucosa during Helicobacter pylori have a T helper cell 1 phenotype. Gastroenterology 114, 482–492 (1998).
pubmed: 9496938 doi: 10.1016/S0016-5085(98)70531-1
Yu, S. et al. Paneth cell multipotency induced by notch activation following injury. Cell Stem Cell 23, 46–59 e45 (2018).
pubmed: 29887318 pmcid: 6035085 doi: 10.1016/j.stem.2018.05.002
Schwitalla, S. et al. Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties. Cell 152, 25–38 (2013).
pubmed: 23273993 doi: 10.1016/j.cell.2012.12.012
Stange, D. E. et al. Differentiated Troy+ chief cells act as reserve stem cells to generate all lineages of the stomach epithelium. Cell 155, 357–368 (2013).
pubmed: 24120136 pmcid: 4094146 doi: 10.1016/j.cell.2013.09.008
Tetteh, P. W. et al. Replacement of lost Lgr5-positive stem cells through plasticity of their enterocyte-lineage daughters. Cell Stem Cell 18, 203–213 (2016).
pubmed: 26831517 doi: 10.1016/j.stem.2016.01.001
Bleuming, S. A. et al. Bone morphogenetic protein signaling suppresses tumorigenesis at gastric epithelial transition zones in mice. Cancer Res. 67, 8149–8155 (2007).
pubmed: 17804727 doi: 10.1158/0008-5472.CAN-06-4659
Torihashi, S. et al. The expression and crucial roles of BMP signaling in development of smooth muscle progenitor cells in the mouse embryonic gut. Differentiation 77, 277–289 (2009).
pubmed: 19272526 doi: 10.1016/j.diff.2008.10.003
Todisco, A. Regulation of gastric metaplasia, dysplasia, and neoplasia by bone morphogenetic protein signaling. Cell. Mol. Gastroenterol. Hepatol. 3, 339–347 (2017).
pubmed: 28462376 pmcid: 5404023 doi: 10.1016/j.jcmgh.2017.01.014
Takabayashi, H. et al. Anti-inflammatory activity of bone morphogenetic protein signaling pathways in stomachs of mice. Gastroenterology 147, 396–406 e397 (2014).
pubmed: 24751878 doi: 10.1053/j.gastro.2014.04.015
Qi, Z. et al. BMP restricts stemness of intestinal Lgr5(+) stem cells by directly suppressing their signature genes. Nat. Commun. 8, 13824 (2017).
pubmed: 28059064 pmcid: 5227110 doi: 10.1038/ncomms13824
Lim, J., Burclaff, J., He, G., Mills, J. C. & Long, F. Unintended targeting of Dmp1-Cre reveals a critical role for Bmpr1a signaling in the gastrointestinal mesenchyme of adult mice. Bone Res. 5, 16049 (2017).
pubmed: 28163952 pmcid: 5282469 doi: 10.1038/boneres.2016.49
Roy, S. A. B. et al. Loss of mesenchymal bone morphogenetic protein signaling leads to development of reactive stroma and initiation of the gastric neoplastic cascade. Sci. Rep. 6, 32759 (2016).
pubmed: 27609464 pmcid: 5016723 doi: 10.1038/srep32759
Parsonnet, J. et al. Helicobacter pylori infection and the risk of gastric carcinoma. N. Engl. J. Med. 325, 1127–1131 (1991).
pubmed: 1891020 doi: 10.1056/NEJM199110173251603
Schreiber, S. et al. The spatial orientation of Helicobacter pylori in the gastric mucus. Proc. Natl Acad. Sci. USA 101, 5024–5029 (2004).
pubmed: 15044704 pmcid: 387367 doi: 10.1073/pnas.0308386101
Bartfeld, S. et al. In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. Gastroenterology https://doi.org/10.1053/j.gastro.2014.09.042 (2014).
Schlaermann, P. et al. A novel human gastric primary cell culture system for modelling Helicobacter pylori infection in vitro. Gut https://doi.org/10.1136/gutjnl-2014-307949 (2014).
Sawai, N. et al. Role of gamma interferon in Helicobacter pylori-induced gastric inflammatory responses in a mouse model. Infect. Immun. 67, 279–285 (1999).
pubmed: 9864227 pmcid: 96308 doi: 10.1128/IAI.67.1.279-285.1999
Sayi, A. et al. The CD4+ T cell-mediated IFN-gamma response to Helicobacter infection is essential for clearance and determines gastric cancer risk. J. Immunol. 182, 7085–7101 (2009).
pubmed: 19454706 doi: 10.4049/jimmunol.0803293
Osaki, L. H. et al. Interferon-gamma directly induces gastric epithelial cell death and is required for progression to metaplasia. J. Pathol. 247, 513–523 (2019).
pubmed: 30511397 pmcid: 6402979 doi: 10.1002/path.5214
Shinohara, M. et al. Bone morphogenetic protein signaling regulates gastric epithelial cell development and proliferation in mice. Gastroenterology 139, 2050–2060 e2052 (2010).
pubmed: 20826155 doi: 10.1053/j.gastro.2010.08.052
Schroder, K., Hertzog, P. J., Ravasi, T. & Hume, D. A. Interferon-gamma: an overview of signals, mechanisms and functions. J. Leukoc. Biol. 75, 163–189 (2004).
pubmed: 14525967 doi: 10.1189/jlb.0603252
Harnack, C. et al. R-spondin 3 promotes stem cell recovery and epithelial regeneration in the colon. Nat. Commun. 10, 4368 (2019).
pubmed: 31554819 pmcid: 6761174 doi: 10.1038/s41467-019-12349-5
Castillo-Azofeifa, D. et al. Atoh1(+) secretory progenitors possess renewal capacity independent of Lgr5(+) cells during colonic regeneration. EMBO J. https://doi.org/10.15252/embj.201899984 (2019).
Gersemann, M. et al. Differences in goblet cell differentiation between Crohn’s disease and ulcerative colitis. Differentiation 77, 84–94 (2009).
pubmed: 19281767 doi: 10.1016/j.diff.2008.09.008
Diosdado, B., van Oort, E. & Wijmenga, C. “Coelionomics”: towards understanding the molecular pathology of coeliac disease. Clin. Chem. Lab. Med. 43, 685–695 (2005).
pubmed: 16207126 doi: 10.1515/CCLM.2005.117
Herring, B. P., Hoggatt, A. M., Burlak, C. & Offermanns, S. Previously differentiated medial vascular smooth muscle cells contribute to neointima formation following vascular injury. Vasc. Cell 6, 21 (2014).
pubmed: 25309723 pmcid: 4193961 doi: 10.1186/2045-824X-6-21
Huang, S. et al. Immune response in mice that lack the interferon-gamma receptor. Science 259, 1742–1745 (1993).
pubmed: 8456301 doi: 10.1126/science.8456301
Muzumdar, M. D., Tasic, B., Miyamichi, K., Li, L. & Luo, L. A global double-fluorescent Cre reporter mouse. Genesis 45, 593–605 (2007).
pubmed: 17868096 doi: 10.1002/dvg.20335
Yan, K. S. et al. The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations. Proc. Natl Acad. Sci. USA 109, 466–471 (2012).
pubmed: 22190486 doi: 10.1073/pnas.1118857109
van Amerongen, R., Bowman, A. N. & Nusse, R. Developmental stage and time dictate the fate of Wnt/beta-catenin-responsive stem cells in the mammary gland. Cell Stem Cell 11, 387–400 (2012).
pubmed: 22863533 doi: 10.1016/j.stem.2012.05.023
Mishina, Y., Hanks, M. C., Miura, S., Tallquist, M. D. & Behringer, R. R. Generation of Bmpr/Alk3 conditional knockout mice. Genesis 32, 69–72 (2002).
pubmed: 11857780 doi: 10.1002/gene.10038
Zuo, X. et al. PPARD and interferon gamma promote transformation of gastric progenitor cells and tumorigenesis in mice. Gastroenterology 157, 163–178 (2019).
pubmed: 30885780 doi: 10.1053/j.gastro.2019.03.018
Stzepourginski, I. et al. CD34+ mesenchymal cells are a major component of the intestinal stem cells niche at homeostasis and after injury. Proc. Natl Acad. Sci. USA 114, E506–E513 (2017).
pubmed: 28074039 pmcid: 5278455 doi: 10.1073/pnas.1620059114
Churchill, G. A. Fundamentals of experimental design for cDNA microarrays. Nat. Genet. 32, 490–495 (2002).
pubmed: 12454643 doi: 10.1038/ng1031

Auteurs

Marta Kapalczynska (M)

Department of Hepatology and Gastroenterology, Charité University Medicine, 13353, Berlin, Germany.
Department of Molecular Biology, Max Planck Institute for Infection Biology, 10117, Berlin, Germany.

Manqiang Lin (M)

Department of Hepatology and Gastroenterology, Charité University Medicine, 13353, Berlin, Germany.
Department of Molecular Biology, Max Planck Institute for Infection Biology, 10117, Berlin, Germany.

Jeroen Maertzdorf (J)

Department of Immunology, Max Planck Institute for Infection Biology, 10117, Berlin, Germany.

Julian Heuberger (J)

Department of Hepatology and Gastroenterology, Charité University Medicine, 13353, Berlin, Germany.
Department of Molecular Biology, Max Planck Institute for Infection Biology, 10117, Berlin, Germany.
ORCID: 0000-0001-7205-732X

Stefanie Muellerke (S)

Department of Hepatology and Gastroenterology, Charité University Medicine, 13353, Berlin, Germany.

Xiangsheng Zuo (X)

Departments of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0002-8593-1132

Ramon Vidal (R)

Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine, 10115, Berlin, Germany.

Imad Shureiqi (I)

Departments of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0003-2019-938X

Anne-Sophie Fischer (AS)

Department of Hepatology and Gastroenterology, Charité University Medicine, 13353, Berlin, Germany.

Sascha Sauer (S)

Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine, 10115, Berlin, Germany.
ORCID: 0000-0002-4794-3693

Hilmar Berger (H)

Department of Hepatology and Gastroenterology, Charité University Medicine, 13353, Berlin, Germany.
Department of Molecular Biology, Max Planck Institute for Infection Biology, 10117, Berlin, Germany.
ORCID: 0000-0002-6304-4946

Evelyn Kidess (E)

Department of Hepatology and Gastroenterology, Charité University Medicine, 13353, Berlin, Germany.

Hans-Joachim Mollenkopf (HJ)

Department of Molecular Biology, Max Planck Institute for Infection Biology, 10117, Berlin, Germany.
ORCID: 0000-0003-1167-4783

Frank Tacke (F)

Department of Hepatology and Gastroenterology, Charité University Medicine, 13353, Berlin, Germany.
ORCID: 0000-0001-6206-0226

Thomas F Meyer (TF)

Department of Molecular Biology, Max Planck Institute for Infection Biology, 10117, Berlin, Germany.
Laboratory of Infection Oncology, Institute of Clinical Molecular Biology (IKMB), Christian Albrechts University of Kiel, Kiel, Germany.
ORCID: 0000-0002-6120-8679

Michael Sigal (M)

Department of Hepatology and Gastroenterology, Charité University Medicine, 13353, Berlin, Germany. michael.sigal@charite.de.
Department of Molecular Biology, Max Planck Institute for Infection Biology, 10117, Berlin, Germany. michael.sigal@charite.de.
Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine, 10115, Berlin, Germany. michael.sigal@charite.de.
Berlin Institute of Health, 10117, Berlin, Germany. michael.sigal@charite.de.
ORCID: 0000-0003-4772-0761

Articles similaires

Evaluating the efficacy of telesurgery with dual console SSI Mantra Surgical Robotic System: experiment on animal model and clinical trials.

Sudhir Prem Srivastava, Vishwajyoti Pascual Srivastava, Avinesh Singh et al.
1.00
Robotic Surgical Procedures Animals Humans Telemedicine Models, Animal

Odour generalisation and detection dog training.

Lyn Caldicott, Thomas W Pike, Helen E Zulch et al.
1.00
Animals Odorants Dogs Generalization, Psychological Smell

Within-subject variation of C-reactive protein and high-sensitivity C-reactive protein: A systematic review and meta-analysis.

Alex Gough, Alice Sitch, Erica Ferris et al.
1.00
C-Reactive Protein Humans Biomarkers Inflammation

Prognostic value of the systemic immune-inflammation index in lung cancer patients receiving immune checkpoint inhibitors: A meta-analysis.

Yanhui Yang, Ji Li, Yi Wang et al.
1.00
Humans Immune Checkpoint Inhibitors Lung Neoplasms Prognosis Inflammation

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › BMP feed-forward loop promotes terminal...
questionsmedicales.fr › Cellules › Cellules épithéliales › BMP feed-forward loop promotes terminal...
questionsmedicales.fr › Tissus › Membranes › Muqueuse › Muqueuse gastrique › BMP feed-forward loop promotes terminal...
questionsmedicales.fr › Infection › Infections bactériennes et mycoses › Infections bactériennes › Infections bactériennes à Gram négatif › Infections à Helicobacter › BMP feed-forward loop promotes terminal...
questionsmedicales.fr › Bactéries › Proteobacteria › Epsilonproteobacteria › Campylobacterales › Helicobacteraceae › Helicobacter › Helicobacter pylori › BMP feed-forward loop promotes terminal...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › BMP feed-forward loop promotes terminal...
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Produits chimiques de laboratoire › Ligands › BMP feed-forward loop promotes terminal...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › BMP feed-forward loop promotes terminal...