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Date: 4 July 2025 (Fri)
Time: 11am - 12:30pm (SGT) Format: Virtual (Zoom Meeting) Host: Yan WANG, Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Army Medical University, China |
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Speaker's information
Shizuka MIURA Division of Stem Cell Medicine, Medical Institute of Bioregulation, Kyushu University, Japan "Conversion of dedifferentiated hepatocytes into intestinal epithelial cells" Pubmed |
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ABSTRACT
It is well known that hepatocytes rapidly lose their function and dedifferentiate into progenitor-like cells in culture. However, the mechanisms underlying both the induction and maintenance of this dedifferentiated state, as well as the differentiation potential of hepatocyte-derived dedifferentiated cells, remain poorly understood. To investigate the behavior of dedifferentiated hepatocytes in detail, we cultured hepatocytes using our established culture system. Through our study, we have demonstrated that hepatocytes can undergo lineage conversion into intestinal progenitor cells in response to changes in culture conditions. In this seminar, I will discuss the characteristics of dedifferentiated hepatocytes observed under our culture conditions, the mechanisms underlying their dedifferentiation, and the remarkable plasticity exhibited by hepatocytes, as revealed by our findings.
BIO
Shizuka Miura is an Associate Professor at Kyushu University. She successfully generated intestinal progenitor cells from fibroblasts using direct reprogramming when she was a Ph.D. student (Cell Stem Cell, 2017). She earned her Ph.D. from Kyushu University in 2018. Her research continues to focus on endoderm-derived tissues, with the aim of developing new cell production technologies and elucidating disease mechanisms through cell reprogramming and the plasticity of tissue-derived cells.
It is well known that hepatocytes rapidly lose their function and dedifferentiate into progenitor-like cells in culture. However, the mechanisms underlying both the induction and maintenance of this dedifferentiated state, as well as the differentiation potential of hepatocyte-derived dedifferentiated cells, remain poorly understood. To investigate the behavior of dedifferentiated hepatocytes in detail, we cultured hepatocytes using our established culture system. Through our study, we have demonstrated that hepatocytes can undergo lineage conversion into intestinal progenitor cells in response to changes in culture conditions. In this seminar, I will discuss the characteristics of dedifferentiated hepatocytes observed under our culture conditions, the mechanisms underlying their dedifferentiation, and the remarkable plasticity exhibited by hepatocytes, as revealed by our findings.
BIO
Shizuka Miura is an Associate Professor at Kyushu University. She successfully generated intestinal progenitor cells from fibroblasts using direct reprogramming when she was a Ph.D. student (Cell Stem Cell, 2017). She earned her Ph.D. from Kyushu University in 2018. Her research continues to focus on endoderm-derived tissues, with the aim of developing new cell production technologies and elucidating disease mechanisms through cell reprogramming and the plasticity of tissue-derived cells.
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Bin WANG
Chongqing University, China "Chromatin Accessibility: An Essential Role in Gastric Tumorigenesis and Patient Stratification" Pubmed |
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ABSTRACT
Chromatin remodeling is a hallmark of cell lineage commitment and cancer development, yet it remains obscure how chromatin dynamics underlies stepwise tumorigenesis from precancer and informs anti-cancer therapeutics. By decoding a large-scale chromatin accessibility atlas of multistage patient samples, we delineate dynamic epigenetic switches spanning multistep gastric tumorigenesis. A cancer-resembling chromatin state in precancer licenses subsequent tumor initiation. In advanced malignancies, inter-patient heterogeneity stratifies three epigenomic subtypes with distinct sensitivity to neoadjuvant immunotherapy. The proliferative and mesenchymal-inflammatory subtypes are highly responsive, while the pseudo-gastric subtype is intrinsically drug-resistant. Mechanistically, the refractory subtype is featured by a unique gastric secretory phenotype, dictated in part by FOSL2 to maintain an immunosuppressive ecosystem. Inhibition of this phenotype by either FOSL2-depletion or using vonoprazan, a clinically available acid blocker, sensitizes immunotherapy. Collectively, we depict chromatin accessibility dynamics facilitating sequential tumorigenesis from cancer precursor and highlight an epigenomic subtyping immediately translatable to guide immunotherapy and overcome drug resistance.
BIO
Bin Wang received medical training in China and obtained Ph.D. degree under the guidance from Dr. Xiu-Wu Bian. Thereafter, he did postdoc in Beth Israel Deaconess Medical Center at Harvard Medical School in Dr. Wenyi Wei lab. As a physician scientist, he has keen interests in dissecting how systemic, environmental and intrinsic factors may regulate stem cells and cancer in the stomach, by exploiting various experimental models including genetically modified mouse models, patient-derived xenografts, and organoid culture. He has multiple ongoing projects focused on the regulatory roles of epigenetics and posttranslational modifications in the pathogenesis of gastric tumorigenesis, including but not limited to immune evasion and metabolic dysregulation. Moreover, he is conducting several clinical trials to improve neoadjuvant immunochemotherapy of gastric cancer. Through these efforts, he believes that new therapeutic avenues will ultimately be developed and exploited to improve cancer diagnosis and therapy in clinic.
Chromatin remodeling is a hallmark of cell lineage commitment and cancer development, yet it remains obscure how chromatin dynamics underlies stepwise tumorigenesis from precancer and informs anti-cancer therapeutics. By decoding a large-scale chromatin accessibility atlas of multistage patient samples, we delineate dynamic epigenetic switches spanning multistep gastric tumorigenesis. A cancer-resembling chromatin state in precancer licenses subsequent tumor initiation. In advanced malignancies, inter-patient heterogeneity stratifies three epigenomic subtypes with distinct sensitivity to neoadjuvant immunotherapy. The proliferative and mesenchymal-inflammatory subtypes are highly responsive, while the pseudo-gastric subtype is intrinsically drug-resistant. Mechanistically, the refractory subtype is featured by a unique gastric secretory phenotype, dictated in part by FOSL2 to maintain an immunosuppressive ecosystem. Inhibition of this phenotype by either FOSL2-depletion or using vonoprazan, a clinically available acid blocker, sensitizes immunotherapy. Collectively, we depict chromatin accessibility dynamics facilitating sequential tumorigenesis from cancer precursor and highlight an epigenomic subtyping immediately translatable to guide immunotherapy and overcome drug resistance.
BIO
Bin Wang received medical training in China and obtained Ph.D. degree under the guidance from Dr. Xiu-Wu Bian. Thereafter, he did postdoc in Beth Israel Deaconess Medical Center at Harvard Medical School in Dr. Wenyi Wei lab. As a physician scientist, he has keen interests in dissecting how systemic, environmental and intrinsic factors may regulate stem cells and cancer in the stomach, by exploiting various experimental models including genetically modified mouse models, patient-derived xenografts, and organoid culture. He has multiple ongoing projects focused on the regulatory roles of epigenetics and posttranslational modifications in the pathogenesis of gastric tumorigenesis, including but not limited to immune evasion and metabolic dysregulation. Moreover, he is conducting several clinical trials to improve neoadjuvant immunochemotherapy of gastric cancer. Through these efforts, he believes that new therapeutic avenues will ultimately be developed and exploited to improve cancer diagnosis and therapy in clinic.