Polarised epithelial monolayers of the gastric mucosa reveal insights into mucosal homeostasis and defence against infection

Gut
Francesco BoccellatoThomas F Meyer

Abstract

Helicobacter pylori causes life-long colonisation of the gastric mucosa, leading to chronic inflammation with increased risk of gastric cancer. Research on the pathogenesis of this infection would strongly benefit from an authentic human in vitro model. Antrum-derived gastric glands from surgery specimens served to establish polarised epithelial monolayers via a transient air-liquid interface culture stage to study cross-talk with H. pylori and the adjacent stroma. The resulting 'mucosoid cultures', so named because they recapitulate key characteristics of the gastric mucosa, represent normal stem cell-driven cultures that can be passaged for months. These highly polarised columnar epithelial layers encompass the various gastric antral cell types and secrete mucus at the apical surface. By default, they differentiate towards a foveolar, MUC5AC-producing phenotype, whereas Wnt signalling stimulates proliferation of MUC6-producing cells and preserves stemness-reminiscent of the gland base. Stromal cells from the lamina propria secrete Wnt inhibitors, antagonising stem-cell niche signalling and inducing differentiation. On infection with H. pylori, a strong inflammatory response is induced preferentially in the undifferentiated ba...Continue Reading

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Citations

Jul 11, 2019·Current Gastroenterology Reports·Gian M GaluraRichard McCallum
Jun 30, 2019·Biomedicines·Anne-Sophie Fischer, Michael Sigal
Feb 28, 2020·Experimental & Molecular Medicine·Sungjin MinSeung-Woo Cho
Jul 11, 2019·Cell Communication and Signaling : CCS·Wang-Yu CaiQi-Cong Luo
Aug 6, 2020·Frontiers in Microbiology·Wolfgang FischerSteffen Backert
Aug 19, 2020·Nature Materials·Masayuki Fujii, Toshiro Sato
Apr 18, 2019·Development·Emily M HollowayJason R Spence
Jun 27, 2019·Nature Cell Biology·Michael SigalThomas F Meyer
Feb 5, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Özge KayisogluSina Bartfeld
Jan 8, 2021·Frontiers in Immunology·Florian TranPhilip Seibler
Mar 9, 2021·International Journal of Medical Microbiology : IJMM·Amina Iftekhar, Michael Sigal
Mar 9, 2021·Frontiers in Pediatrics·Lauren O'ConnellCarol M Aherne
Mar 7, 2021·International Journal of Molecular Sciences·Daniela ElettoAlessandra Tosco
Apr 4, 2021·International Journal of Molecular Sciences·Lornella SeeneevassenChristine Varon
May 7, 2021·Gastroenterology·Sarah WölfflingFrancesco Boccellato
Jun 11, 2021·Cell Host & Microbe·Jens PuschhofHans Clevers
Jul 25, 2021·International Journal of Molecular Sciences·Joseph AzarWassim Abou-Kheir
Jul 13, 2021·Inflammatory Bowel Diseases·Babajide A OjoMichael J Rosen
Dec 24, 2020·Trends in Biotechnology·Phatcharida JantareeMichael Naumann
Aug 21, 2021·Frontiers in Cardiovascular Medicine·Xinyi ShenZhongqun Wang
Aug 28, 2021·International Journal of Molecular Sciences·Claudia GüntherBeate Winner

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Methods Mentioned

BETA
reverse transcription PCR
electron microscopy
PCR

Software Mentioned

MaxQuant

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