Helicobacter pylori shows tropism to gastric differentiated pit cells dependent on urea chemotaxis

Aguilar, Carmen; Paužuolis, Mindaugas; Pompaiah, Malvika; Vafadarnejad, Ehsan; Arampatzi, Panagiota; Fischer, Mara; Narres, Dominik; Neyazi, Mastura; Kayisoglu, Özge; Sell, Thomas; Blüthgen, Nils; Morkel, Markus; Wiegering, Armin; Germer, Christoph‐Thomas; Kircher, Stefan; Rosenwald, Andreas; Bartfeld, Sina

doi:10.1038/s41467-022-33165-4

Cited by 15 publications

(13 citation statements)

References 68 publications

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“…Although a large number of in vitro studies have explored its aberrant effects on host cells, for a long time it was not clear which cells can be targeted by H. pylori in vivo. In a recent publication, Aguilar and colleagues showed that H. pylori are capable of binding with high affinity to differentiated gastric pit cells expressing high levels of gastrokine 1 and 2 (GKN1-GKN2) (20). This is in line with clinical studies showing that in human samples H. pylori is also detected in that region.…”

Section: H Pylori Exploit Specific Features That Allow Gland Coloniza...mentioning

confidence: 60%

“…H. pylori express several chemoreceptors, such as TlpA, TlpB, TlpC and TlpD. TlpB is able to sense the chemoattractant urea, and activation of the downstream signaling is thought to be important for sensing epithelial cells (20,25). TlpA, TlpB and TlpD act as acid sensors, with acid being a chemorepellent.…”

Section: H Pylori Exploit Specific Features That Allow Gland Coloniza...mentioning

confidence: 99%

“…The ability of H. pylori to colonize and directly interact with the epithelium is crucial to the pathogenesis caused by these bacteria. Imaging studies have demonstrated that H. pylori are found in the gastric mucus layer in close association with mucous pit cells and H. pylori have been found to possess specific molecular mechanisms to locate these cells (20). However, pit cells are short-lived and terminally differentiated, thus their interplay with H. pylori is unlikely to cause long-term pathology.…”

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confidence: 99%

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Unwelcome guests – the role of gland-associated Helicobacter pylori infection in gastric carcinogenesis

Beccaceci

Sigal

2023

Front. Oncol.

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Helicobacter pylori (H. pylori) are Gram-negative bacteria that cause chronic gastritis and are considered the main risk factor for the development of gastric cancer. H. pylori have evolved to survive the harsh luminal environment of the stomach and are known to cause damage and signaling aberrations in gastric epithelial cells, which can result in premalignant and malignant pathology. As well as colonizing the gastric mucus and surface epithelial cells, a subpopulation of H. pylori can invade deep into the gastric glands and directly interact with progenitor and stem cells. Gland colonization therefore bears the potential to cause direct injury to long-lived cells. Moreover, this bacterial subpopulation triggers a series of host responses that cause an enhanced proliferation of stem cells. Here, we review recent insights into how gastric gland colonization by H. pylori is established, the resulting pro-carcinogenic epithelial signaling alterations, as well as new insights into stem cell responses to infection. Together these point towards a critical role of gland-associated H. pylori in the development of gastric cancer.

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Section: H Pylori Exploit Specific Features That Allow Gland Coloniza...mentioning

confidence: 60%

Section: H Pylori Exploit Specific Features That Allow Gland Coloniza...mentioning

confidence: 99%

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confidence: 99%

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Unwelcome guests – the role of gland-associated Helicobacter pylori infection in gastric carcinogenesis

Beccaceci

Sigal

2023

Front. Oncol.

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“…Hp preferentially colonizes antral cell types such as pit cells [55] causing mucosal atrophy and IM [38,56]. As atrophy/IM progresses, Hp levels often decrease due to IM cells being less hospitable to infection [57], raising the possibility that IM may function a protective mechanism against Hp.…”

Section: Discussionmentioning

confidence: 99%

Spatiotemporal Genomic Profiling of Intestinal Metaplasia Reveals Clonal Dynamics of Gastric Cancer Progression

Huang

Uchihara

et al. 2023

Preprint

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Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. We analyzed 1256 gastric samples (1152 IMs) from 692 subjects through a prospective 10-year study. We identified 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9), largely occurring as small clonal events. Analysis of clonal dynamics between and within subjects, and also longitudinally across time, revealed that IM clones are likely transient but increase in size upon progression to dysplasia, with eventual transmission of somatic events to paired GCs. Single-cell and spatial profiling highlighted changes in tissue ecology and lineage heterogeneity in IM, including an intestinal stem-cell dominant cellular compartment linked to early malignancy. Expanded transcriptome profiling revealed expression-based molecular subtypes of IM, including a body-resident "pseudoantralized" subtype associated with incomplete histology, antral/intestinal cell types, ARID1A mutations, inflammation, and microbial communities normally associated with the healthy oral tract. We demonstrate that combined clinical-genomic models outperform clinical-only models in predicting IMs likely to progress. Our results raise opportunities for GC precision prevention and interception by highlighting strategies for accurately identifying IM patients at high GC risk and a role for microbial dysbiosis in IM progression.

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“…successfully established Helicobacter pylori (Hp)‐infected human gastric organoids, and inflammatory responses were observed in these infected organoid cells. The adhesion of Hp depends on the high affinity between the TlpB receptor and urea secreted by gastric cells, and Hp is likely to attach to highly differentiated pit cells with a larger volume 184 . Furthermore, the CagA factor derived from Hp was transferred into organoid cells, leading to activation of certain pathways and increased cell proliferation 50,184 .…”

Section: Biomedical Applications Of Organoidsmentioning

confidence: 99%

Organoids: The current status and biomedical applications

Yang

Kung

et al. 2023

MedComm

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Organoids are three‐dimensional (3D) miniaturized versions of organs or tissues that are derived from cells with stem potential and can self‐organize and differentiate into 3D cell masses, recapitulating the morphology and functions of their in vivo counterparts. Organoid culture is an emerging 3D culture technology, and organoids derived from various organs and tissues, such as the brain, lung, heart, liver, and kidney, have been generated. Compared with traditional bidimensional culture, organoid culture systems have the unique advantage of conserving parental gene expression and mutation characteristics, as well as long‐term maintenance of the function and biological characteristics of the parental cells in vitro. All these features of organoids open up new opportunities for drug discovery, large‐scale drug screening, and precision medicine. Another major application of organoids is disease modeling, and especially various hereditary diseases that are difficult to model in vitro have been modeled with organoids by combining genome editing technologies. Herein, we introduce the development and current advances in the organoid technology field. We focus on the applications of organoids in basic biology and clinical research, and also highlight their limitations and future perspectives. We hope that this review can provide a valuable reference for the developments and applications of organoids.

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Helicobacter pylori shows tropism to gastric differentiated pit cells dependent on urea chemotaxis

Cited by 15 publications

References 68 publications

Unwelcome guests – the role of gland-associated Helicobacter pylori infection in gastric carcinogenesis

Unwelcome guests – the role of gland-associated Helicobacter pylori infection in gastric carcinogenesis

Spatiotemporal Genomic Profiling of Intestinal Metaplasia Reveals Clonal Dynamics of Gastric Cancer Progression

Organoids: The current status and biomedical applications

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