Article
Gastroenterology & Hepatology
Brianna Caldwell, Anne R. Meyer, Jared A. Weis, Amy C. Engevik, Eunyoung Choi
Summary: Our study provides pivotal evidence for cell plasticity and lineage contributions from differentiated gastric chief cells during acute metaplasia development. Mature chief cells, rather than isthmal progenitor cells, serve as the predominant origin of SPEM cells during the metaplastic process after acute mucosal injury. Furthermore, long-term label-retaining chief cells can be identified, with only a very small subset displaying reprogramming ability in homoeostasis.
Editorial Material
Oncology
James R. Goldenring
Summary: Intestinal-type gastric cancer can arise from precancerous metaplastic lineages, specifically from spasmolytic polypeptide-expressing metaplasia (SPEM) cells. A recent study identified an activating Kras(G12D) mutation in SPEM cells, which propagated into adenomatous and cancerous lesions, suggesting that SPEM lineages can serve as a direct precursor for dysplasia and intestinal-type gastric cancer.
JOURNAL OF PATHOLOGY
(2023)
Article
Gastroenterology & Hepatology
Su-Hyung Lee, Ela W. Contreras Panta, David Gibbs, Yoonkyung Won, Jimin Min, Changqing Zhang, Joseph T. Roland, Se-Hoon Hong, Yoojin Sohn, Evan Krystofiak, Bogun Jang, Lorenzo Ferri, Veena Sangwan, Jiannis Ragoussis, Sophie Camilleri-Broet, Joseph Caruso, Chira Chen-Tanyolac, Michael Strasser, Philippe Gascard, Thea D. Tlsty, Sui Huang, Eunyoun Choi, James R. Goldenring
Summary: In this study, the researchers identified the cellular heterogeneity of fibroblasts in gastric cancer patients using single-cell transcriptomics. They found that the expression differences of PDGFRA, FBLN2, ACTA2, and PDGFRB can categorize fibroblasts into four subsets, which exhibit distinctive distribution patterns in different pathologic stages. The study also demonstrated that the association between fibroblasts and epithelial cells can promote the direct transition of metaplastic cell lineages into dysplastic lineages. These findings provide important insights into the development of gastric cancer.
Article
Cell Biology
Yongji Zeng, Qing K. Li, Sujayita Roy, Jason C. Mills, Ramon U. Jin
Summary: Plasticity is an important property of the gastrointestinal tract and plays a role in both normal response to injury and cancer development. This study focuses on the development of gastric and esophageal cancers from intestinal metaplasia, and findings indicate that Barrett's esophagus exhibits incomplete intestinal metaplasia with concurrent expression of gastric and intestinal traits. Understanding the molecular pathways involved in the development of these cancers will lead to improved diagnostic and therapeutic approaches.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell & Tissue Engineering
Ji-Hyun Lee, Somi Kim, Seungmin Han, Jimin Min, Brianna Caldwell, Aileen-Diane Bamford, Andreia Sofia Batista Rocha, JinYoung Park, Sieun Lee, Szu-Hsien Sam Wu, Heetak Lee, Juergen Fink, Sandra Pilat-Carotta, Jihoon Kim, Manon Josserand, Reka Szep-Bakonyi, Yohan An, Young Seok Ju, Anna Philpott, Benjamin D. Simons, Daniel E. Stange, Eunyoung Choi, Bon-Kyoung Koo, Jong Kyoung Kim
Summary: This study identified p57 as a molecular switch for maintaining the reserve stem cell state in chief cells of the stomach. p57 expression is constantly maintained in chief cells during homeostasis but rapidly diminishes after injury, leading to robust proliferation. Overexpression of p57 induces a long-term reserve stem cell state accompanied by altered niche requirements and a mature chief cell phenotype. However, constitutive expression of p57 impairs the injury response of chief cells.
Article
Immunology
Samaneh Saberi, Maryam Esmaeili, Mohammad Tashakoripour, Mahmoud Eshagh Hosseini, Hossein Baharvand, Marjan Mohammadi
Summary: This study evaluated the expression patterns of candidate genes induced by H. pylori infection and found that it caused regulatory changes in genes related to gastric-to-intestinal transdifferentiation. These changes included upregulation of self-renewal and pluripotency factors and aberrant expression of intestine-specific transcription factors, further promoting the process of transdifferentiation. These findings may contribute to a better understanding of the mechanism of gastric-to-intestinal transdifferentiation.
MICROBIAL PATHOGENESIS
(2022)
Article
Medicine, General & Internal
Lifeng Liu, Lin Han, Qingzhu Ma, Jinliang Zhang
Summary: Gastric adenocarcinoma of fundic gland (chief cell predominant type) is a rare variant characterized by mild nuclear atypia and specific immunohistochemical markers, often coexisting with well-differentiated tubular adenocarcinoma. It presents in the deep mucosal layer and muscularis mucosa, undetectable by endoscopy but discernible in pathology with mild nuclear atypia and special biomarkers.
Article
Gastroenterology & Hepatology
Massimo Rugge, Diana Sacchi, Robert M. Genta, Francesca Zanco, Stefano Guzzinati, Marco Pizzi, Matteo Fassan, Antonio Di Sabatino, Hashem El-Serag
Summary: This study found that pathologists consistently assessed PPM whether using H&E staining or TFF2-IHC. The agreement among observers may be higher when assessing PPM based on TFF2-IHC.
DIGESTIVE AND LIVER DISEASE
(2021)
Article
Gastroenterology & Hepatology
Yasuhiro Wada, Ken-ichi Mukaisho, Shunpei Kanai, Takahisa Nakayama, Masahide Fukuda, Kazuhiro Mizukami, Tadayoshi Okimoto, Masaaki Kodama, Hiroyuki Sugihara, Kazunari Murakami, Ryoji Kushima
Summary: This study investigated the characteristics and histogenesis of pancreatic acinar cell metaplasia (PACM) using a duodenal contents reflux model. The results showed that PACM cells exhibited pancreatic acinar cell morphology under electron microscopy and may originate from stem cells in the neck of oxyntic glands. Double fluorescent staining identified early lesions of PACM as double positive for α-amylase and TFF2.
DIGESTIVE DISEASES AND SCIENCES
(2021)
Article
Gastroenterology & Hepatology
Jonathan T. Busada, Kylie N. Peterson, Stuti Khadka, Xiaojiang Xu, Robert H. Oakley, Donald N. Cook, John A. Cidlowski
Summary: Glucocorticoids and androgens work together to regulate gastric inflammation, with androgen signaling within ILC2s preventing their pathogenic activation by suppressing proinflammatory cytokine transcription. This highlights a critical role for sex hormones in regulating gastric inflammation and metaplasia.
Article
Gastroenterology & Hepatology
Min Zhang, Shuofeng Hu, Min Min, Yanli Ni, Zheng Lu, Xiaotian Sun, Jiaqi Wu, Bing Liu, Xiaomin Ying, Yan Liu
Summary: This study utilized single-cell RNA sequencing to uncover molecular and cellular heterogeneity in gastric adenocarcinoma, identifying different cell subgroups with diverse differentiation degrees that may predict prognosis. Some subgroups corresponded to histopathological features, while others exhibited unique transcriptome profiles. Additionally, evidence was provided for potential transition from gastric chief cells into metaplasia expressing spasmolytic polypeptides.
Review
Cell Biology
Zilin Deng, Jiaxing Zhu, Zhiyuan Ma, Zhiqiang Yi, Biguang Tuo, Taolang Li, Xuemei Liu
Summary: Diffuse gastric mucosal injury is a chronic injury characterized by altered cell differentiation, including spasmolytic polypeptide expression metaplasia (SPEM) and intestinal metaplasia (IM), which are considered precancerous lesions of gastric cancer (GC). Recent evidence suggests that initial chief cell loss is sufficient to induce gastric mucosal injury and ultimately lead to GC. This provides a novel perspective for the prevention and treatment of diffuse gastric mucosal injury.
CELL DEATH DISCOVERY
(2023)
Article
Oncology
Ruiping Wang, Shumei Song, Jiangjiang Qin, Katsuhiro Yoshimura, Fuduan Peng, Yanshuo Chu, Yuan Li, Yibo Fan, Jiankang Jin, Minghao Dang, Enyu Dai, Guangsheng Pei, Guangchun Han, Dapeng Hao, Yating Li, Deyali Chatterjee, Kazuto Harada, Melissa Pool Pizzi, Ailing W. Scott, Ghia Tatlonghari, Xinmiao Yan, Zhiyuan Xu, Can Hu, Shaowei Mo, Namita Shanbhag, Yang Lu, Matheus Sewastjanow-Silva, Ahmed Adel Fouad Abdelhakeem, Guang Peng, Samir M. Hanash, George A. Calin, Cassian Yee, Pawel Mazur, Autumn N. Marsden, Andrew Futreal, Zhenning Wang, Xiangdong Cheng, Jaffer A. Linghua, Linghua Wang
Summary: In this study, single-cell profiling was performed to understand the reprogramming of tumor microenvironment (TME) in gastric adenocarcinoma (GAC) progression. The results showed that immunosuppressive myeloid and stromal subsets dominate late-stage GACs, while abundant IgA+ plasma cells exist in the premalignant microenvironment. Six TME ecotypes were identified, each with different distributions in different tissues and stages of GAC. The study provides a high-resolution GAC TME atlas and potential therapeutic targets for further investigation.
Article
Nutrition & Dietetics
Shaima Sirajudeen, Iltaf Shah, Sherif M. Karam, Asma Al Menhali
Summary: Vitamin D deficiency can result from insufficient light exposure or intake. This study investigated the biological effects of vitamin D deficiency on mouse gastric glands and found that the effects were influenced by the severity of deficiency. Unique gastric phenotypes were observed in mice with light-induced vitamin D deficiency compared to diet-induced deficiency.
Review
Biochemistry & Molecular Biology
Paulius Jonaitis, Limas Kupcinskas, Juozas Kupcinskas
Summary: Gastric cancer is a common cause of mortality worldwide, with intestinal metaplasia considered a key factor in its development. Recent research has identified various molecular alterations in intestinal metaplasia, some of which show strong associations with the disease and potential for prevention and treatment, though study homogeneity is a key limiting factor.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Gastroenterology & Hepatology
James R. Goldenring, Jason C. Mills
Summary: The mucosa of the body of the stomach uses depth-dependent mechanisms to respond to injury, leading to various histopathological changes and potential progression to dysplasia and cancer. This metaplasia process is broadly conserved across tissues and species, involving specific cytokines in facilitating the reprogramming of cells into different types, with implications for diagnostic and clinical purposes.
Article
Gastroenterology & Hepatology
Zhibo Ma, Nikki K. Lytle, Bob Chen, Nidhi Jyotsana, Sammy Weiser Novak, Charles J. Cho, Leah Caplan, Olivia Ben-Levy, Abigail C. Neininger, Dylan T. Burnette, Vincent Q. Trinh, Marcus C. B. Tan, Emilee A. Patterson, Rafael Arrojo E. Drigo, Rajshekhar R. Giraddi, Cynthia Ramos, Anna L. Means, Ichiro Matsumoto, Uri Manor, Jason C. Mills, James R. Goldenring, Ken S. Lau, Geoffrey M. Wahl, Kathleen E. DelGiorno
Summary: Under chronic injury conditions, acinar cells undergo a pyloric-type metaplasia to mucinous progenitor-like populations, which seed disparate tuft cell and enteroendocrine cell lineages. ADM-derived enteroendocrine cell subtypes are diverse. Expression of Kras(G12D) is sufficient to drive neoplasia when targeted to injury-induced ADM populations, providing an alternative origin for tumorigenesis. This program is conserved in human pancreatitis, shedding light on early events in pancreatic diseases.
Article
Medicine, Research & Experimental
Jose B. Saenz, Nancy Vargas, Charles J. Cho, Jason C. Mills
Summary: Cells can recognize both foreign and host-derived dsRNA through a signaling pathway, with ADAR1 playing a central role in regulating dsRNA response. The dsRNA response is cell intrinsic, epithelium-autonomous, and independent of interferon signaling. Furthermore, dsRNA accumulates in chief cells during gastric metaplasia, and ADAR1 is required for chief cells to reenter the cell cycle during metaplasia. These findings suggest that cell-intrinsic ADAR1 signaling is critical for the induction of metaplasia and may be involved in oncogenesis.
Meeting Abstract
Biochemistry & Molecular Biology
Jason Mills
Article
Gastroenterology & Hepatology
Vani Konda, Rhonda F. Souza, Kerry B. Dunbar, Jason C. Mills, Daniel S. Kim, Robert D. Odze, Stuart J. Spechler
Summary: This study aimed to characterize the early endoscopic and histologic features of radiofrequency ablation (RFA) wound healing in patients with Barrett's esophagus (BE). The results showed that squamous re-epithelialization of RFA wounds not only progressed through squamous cells extending from the proximal wound edge, but also through islands of squamous epithelium sprouting throughout the ablated segment. Additionally, subepithelial glandular structures associated with the squamous islands were found to increase post-RFA. Furthermore, subsquamous intestinal metaplasia (SSIM) was detected in biopsies of patients during the healing process. This study provides insights into the mechanisms of esophageal metaplasia and the healing of RFA wounds.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Cell Biology
Mahliyah Adkins-Threats, Jason C. Mills
Summary: Recent studies have discovered that adult organs recruit progenitor cells to regenerate tissues after injury using cell plasticity programs, and plasticity is more common than previously believed, even in homeostasis. This article focuses on the interplay between normal stem cell differentiation and plasticity in homeostasis and after injury, using the gastric epithelium as an example. It also examines the common features of regenerative programs and discusses how evolutionarily conserved plasticity programs can help us understand pathological processes.
CURRENT OPINION IN GENETICS & DEVELOPMENT
(2022)
Editorial Material
Gastroenterology & Hepatology
Charles J. Cho, Jason C. Mills
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Medicine, Research & Experimental
Saeed Soleymanjahi, Valerie Blanc, Elizabeth A. Molitor, David M. Alvarado, Yan Xie, Vered Gazit, Jeffrey W. Brown, Kathleen Byrnes, Ta-Chiang Liu, Jason C. Mills, Matthew A. Ciorba, Deborah C. Rubin, Nicholas O. Davidson
Summary: RNA-binding protein 47 (RBM47) plays an important role in embryonic endoderm development, and this study found that it also has implications in adult intestine function. Knockout mice lacking Rbm47 showed increased cell proliferation and abnormal morphology in the intestine, while Rbm47-deficient mice were protected against colitis-associated cancer. The findings suggest that RBM47 is a cell-intrinsic modifier of intestinal growth, inflammatory, and tumorigenic pathways.
Article
Cell Biology
Yongji Zeng, Qing K. Li, Sujayita Roy, Jason C. Mills, Ramon U. Jin
Summary: Plasticity is an important property of the gastrointestinal tract and plays a role in both normal response to injury and cancer development. This study focuses on the development of gastric and esophageal cancers from intestinal metaplasia, and findings indicate that Barrett's esophagus exhibits incomplete intestinal metaplasia with concurrent expression of gastric and intestinal traits. Understanding the molecular pathways involved in the development of these cancers will lead to improved diagnostic and therapeutic approaches.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Gastroenterology & Hepatology
Spencer G. Willet, Nattapon Thanintorn, Helen McNeill, Sung-Ho Huh, David M. Ornitz, Won Jae Huh, Stella G. Hoft, Richard J. DiPaolo, Jason C. Mills
Summary: Acute and chronic gastric injury can lead to pyloric metaplasia, which is characterized by the death of parietal cells and the reprogramming of chief cells into proliferative, mucin-rich metaplasia cells. The transcription factor SOX9 has been identified as a potential regulator of mucous neck and metaplasia cell identity in the stomach. SOX9 is expressed in early gastric progenitors and mature mucous neck cells, and its misexpression can lead to an expansion of mucous gene expression in the gastric epithelium.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Xiaobo Lin, Jason C. Mills, Jeffrey W. Brown
Meeting Abstract
Gastroenterology & Hepatology
Spencer G. Willet, Jason Mills
Meeting Abstract
Gastroenterology & Hepatology
Ramon Jin, Jean S. Wang, Qing K. Li, Jason Mills
Meeting Abstract
Gastroenterology & Hepatology
Xiaobo Lin, Yan Kefalov, Ramon Jin, Jason Mills, Jeffrey W. Brown
Meeting Abstract
Gastroenterology & Hepatology
Charles J. Cho, Jason Mills
