Long-term in vitro expansion of a human fetal pancreas stem cell that generates all three pancreatic cell lineages 公告 2024-12-02 14:53:03 Written By Kym Kilbourne Title: Long-term in vitro expansion of a human fetal pancreas stem cell that generates all three pancreatic cell lineages Research Background and Significance The pancreas, an organ with dual functions of digestion and blood sugar control, is crucial for understanding related diseases. However, most organoids consist of only one type of cell, limiting the understanding of the pancreas's overall function. Therefore, constructing organoids that include all pancreatic cell types is of great significance for in-depth study of pancreatic development and function. Research Introduction On December 2, 2024, Professor Hans Clevers and his team published a research paper titled "Long-term in vitro expansion of a human fetal pancreas stem cell that generates all three pancreatic cell lineages" in the journal "Cell". The study successfully constructed a new type of pancreatic organoid—human fetal pancreas organoids (hfPO)—which includes all three key cell types in the pancreas: acinar cells, ductal cells, and endocrine cells. Additionally, the study discovered a new type of tripotent stem cell expressing the LGR5 protein, which can differentiate into the three key cell types of the pancreas. Research Highlights Long-term in vitro expansion: Researchers successfully established 18 human fetal pancreas organoid (hfPO) lines from human fetal pancreas samples aged 8 to 17 weeks and demonstrated that these organoids can be expanded in vitro for a long term (over 2 years). Trilineage differentiation potential: These hfPOs can differentiate into the three main pancreatic cell lineages: acinar cells, ductal cells, and endocrine cells. LGR5 as a stem cell marker: The study found that LGR5-marked cells are tripotent stem/progenitor cells that also exist in adult gastrointestinal tracts, indicating their key role in maintaining tissue regeneration. Research Results Establishment and long-term expansion of hfPO: The research team successfully established 18 human fetal pancreas organoid (hfPO) lines from human fetal pancreas samples aged 8 to 17 weeks. Among them, 4 hfPOs from samples aged 15 to 16 weeks could exponentially expand and stably maintain over 2 years under optimized culture conditions. These hfPOs can produce all three types of pancreatic cells: acinar cells, ductal cells, and endocrine cells. Discovery of LGR5+ tripotent stem cells: Through single-cell RNA sequencing technology, researchers discovered rare new stem cells expressing the LGR5 protein in fetal pancreas and hfPOs, known as LGR5+ tripotent stem cells. These LGR5+ cells share multiple biomarkers with adult gastrointestinal tract stem cells, indicating they may have similar stem cell characteristics. Trilineage differentiation potential of LGR5+ cells: The study showed that organoids derived from single LGR5+ organoid-originated cells have the unique ability to develop into all three types of pancreatic cell types in vitro. These organoids can differentiate into functional acinar and endocrine cell lineages and can perform the expected functions of these cell types. New insights into pancreatic development: The study provides new information about the duration of human fetal pancreatic stem cells, suggesting they may exist longer than observed in mouse studies. Organoids grown from these stem cells can grow rapidly over several years while still being able to produce the three main cell types in the pancreas. Differences in pancreatic development between humans and mice: The study also discovered a key difference in pancreatic development between mice and humans: the LGR5 protein can mark stem cells in different tissues, and this protein is only present in human pancreatic stem cells, not in mice. This finding emphasizes the importance of studying human biology, as animal models may not reveal such species differences. Research Significance Professor Hans Clevers' team's research has constructed a new type of organoid that models the fetal pancreas, providing researchers with a new method to study how genetics and environment affect pancreatic development and health. The study of these organoids can help develop regenerative therapies and new drugs for pancreatic diseases, which is of great significance for advancing medical research and treatment. Paper Link https://www.cell.com/cell/fulltext/S0092-8674(24)01254-6 Kym Kilbourne
Long-term in vitro expansion of a human fetal pancreas stem cell that generates all three pancreatic cell lineages 公告 2024-12-02 14:53:03 Written By Kym Kilbourne Title: Long-term in vitro expansion of a human fetal pancreas stem cell that generates all three pancreatic cell lineages Research Background and Significance The pancreas, an organ with dual functions of digestion and blood sugar control, is crucial for understanding related diseases. However, most organoids consist of only one type of cell, limiting the understanding of the pancreas's overall function. Therefore, constructing organoids that include all pancreatic cell types is of great significance for in-depth study of pancreatic development and function. Research Introduction On December 2, 2024, Professor Hans Clevers and his team published a research paper titled "Long-term in vitro expansion of a human fetal pancreas stem cell that generates all three pancreatic cell lineages" in the journal "Cell". The study successfully constructed a new type of pancreatic organoid—human fetal pancreas organoids (hfPO)—which includes all three key cell types in the pancreas: acinar cells, ductal cells, and endocrine cells. Additionally, the study discovered a new type of tripotent stem cell expressing the LGR5 protein, which can differentiate into the three key cell types of the pancreas. Research Highlights Long-term in vitro expansion: Researchers successfully established 18 human fetal pancreas organoid (hfPO) lines from human fetal pancreas samples aged 8 to 17 weeks and demonstrated that these organoids can be expanded in vitro for a long term (over 2 years). Trilineage differentiation potential: These hfPOs can differentiate into the three main pancreatic cell lineages: acinar cells, ductal cells, and endocrine cells. LGR5 as a stem cell marker: The study found that LGR5-marked cells are tripotent stem/progenitor cells that also exist in adult gastrointestinal tracts, indicating their key role in maintaining tissue regeneration. Research Results Establishment and long-term expansion of hfPO: The research team successfully established 18 human fetal pancreas organoid (hfPO) lines from human fetal pancreas samples aged 8 to 17 weeks. Among them, 4 hfPOs from samples aged 15 to 16 weeks could exponentially expand and stably maintain over 2 years under optimized culture conditions. These hfPOs can produce all three types of pancreatic cells: acinar cells, ductal cells, and endocrine cells. Discovery of LGR5+ tripotent stem cells: Through single-cell RNA sequencing technology, researchers discovered rare new stem cells expressing the LGR5 protein in fetal pancreas and hfPOs, known as LGR5+ tripotent stem cells. These LGR5+ cells share multiple biomarkers with adult gastrointestinal tract stem cells, indicating they may have similar stem cell characteristics. Trilineage differentiation potential of LGR5+ cells: The study showed that organoids derived from single LGR5+ organoid-originated cells have the unique ability to develop into all three types of pancreatic cell types in vitro. These organoids can differentiate into functional acinar and endocrine cell lineages and can perform the expected functions of these cell types. New insights into pancreatic development: The study provides new information about the duration of human fetal pancreatic stem cells, suggesting they may exist longer than observed in mouse studies. Organoids grown from these stem cells can grow rapidly over several years while still being able to produce the three main cell types in the pancreas. Differences in pancreatic development between humans and mice: The study also discovered a key difference in pancreatic development between mice and humans: the LGR5 protein can mark stem cells in different tissues, and this protein is only present in human pancreatic stem cells, not in mice. This finding emphasizes the importance of studying human biology, as animal models may not reveal such species differences. Research Significance Professor Hans Clevers' team's research has constructed a new type of organoid that models the fetal pancreas, providing researchers with a new method to study how genetics and environment affect pancreatic development and health. The study of these organoids can help develop regenerative therapies and new drugs for pancreatic diseases, which is of great significance for advancing medical research and treatment. Paper Link https://www.cell.com/cell/fulltext/S0092-8674(24)01254-6 Kym Kilbourne
