New insights into the regulation of gastric stem cell differentiation

Researchers from the Nara Institute of Science and Technology (NAIST), Japan, led by Hitomi Takada and Akira Kurisaki, have made significant progress in understanding the mechanisms underlying the renewal and differentiation of stem cells in the gastric corpus, a vital part of the glandular stomach. Their findings were recently published in Nature Communications.

The team employed advanced techniques, including Quartz-Seq2, a precise single-cell RNA sequencing technology developed by RIKEN, along with in vitro gastric assays and in vivo experiments using mouse models. This combined approach enabled them to analyze the gene expression dynamics during stem cell differentiation into different gastric cell lineages.

Through their comprehensive study, the researchers identified two signaling pathways involved in stem cell differentiation. They discovered that the transforming growth factor alpha-epidermal growth factor receptor-extracellular signal-regulated kinase (TGFɑ-EGFR-ERK) signaling pathway plays a crucial role in the differentiation of stem cells into mucus-secreting pit cells. Additionally, they found that the tumor necrosis factor ligand superfamily member 12-nuclear factor kappa light chain enhancer of activated B cell (TNFSF12-NF-κB) signaling pathway helps maintain gastric epithelial cells in an undifferentiated state.

Notably, the team observed that inhibiting the EGFR pathway resulted in a reduced production of pit cells, indicating the pathway’s necessity for stem cell differentiation in mice. This finding contradicted previous knowledge that associated EGFR signaling with cancer development, suggesting a differentiation-promoting role in healthy gastric homeostasis.

The researchers view this study as a significant step toward unraveling the mechanisms governing cellular homeostasis in a healthy stomach. With this foundational knowledge, they plan to explore the involvement of these pathways in other gastrointestinal diseases.

The team is optimistic about future prospects and the potential impact of their research. By elucidating the regulatory framework of TGFα-EGFR-ERK and TNFSF12-NF-κB in maintaining healthy stomach epithelial homeostasis, they have set the stage for investigating mechanisms underlying various gastrointestinal disorders.

Source: Nara Institute of Science and Technology

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