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Date: 2 Sep 2025 (Tuesday)
Time: 11am - 12:30pm (SGT) Format: Virtual (Zoom Meeting) Hosts: Lin LIN, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, China Jonathan Yuin-Han LOH, Institute of Molecular and Cell Biology, Singapore |
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Speakers' information
Yi Arial ZENG Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, China "Harnessing adult stem cells for pancreatic islet regeneration" Pubmed |
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ABSTRACT
Pancreatic β cells are the sole producers of insulin in humans and nearly all other vertebrates. However, generating functional β cells in vitro has proven to be a challenging task. Our recent study identified a Procr+ cell population within adult mouse pancreatic islets. These cells lack differentiation markers and exhibit characteristics of epithelial-to-mesenchymal transition (EMT). Through genetic lineage tracing, we discovered that Procr islet cells undergo clonal expansion and generate all four endocrine cell types during adult homeostasis. When isolated, Procr cells, which comprise approximately 1% of islet cells, can form islet-like organoids when cultured at clonal density. These organoids can be exponentially expanded over extended periods through serial passaging, with differentiation inducible at any point in the culture. The differentiated islet organoids consist of all endocrine cell types of the islet and are glucose-responsive for insulin secretion. When transplanted into diabetic mice, the islet organoids effectively restore normoglycemia. Our findings demonstrate the presence of a population of resident stem/progenitor cells within the adult pancreatic islet. We will also further discuss the relevance of these progenitors in islet development and their potential to stimulate islet regeneration.
BIO
Yi Arial Zeng is a Principal Investigator at the Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences. She obtained her Ph.D. from Simon Fraser University in Canada and completed her postdoctoral training at Stanford University. Her research focuses on understanding the regulatory mechanisms of adult stem cells across various tissues and their interactions with the surrounding niche. She has concentrated her efforts on Procr (protein C receptor), a target of Wnt and Yap signaling pathways, which has been identified as a surface marker for adult stem cells in multiple tissues, including the mammary gland, blood vessel endothelium, hematopoietic system, and ovarian epithelium. Her recent work uncovers a unique pancreatic islet resident stem/progenitor cell population in adult mouse and establishes a method to expand these cells and differentiate them in vitro into functional islet organoids. This research lays the groundwork for exploring islet regeneration in situ and exploited for the expansion and induction of functional β cells in vitro for the treatment of diabetes. Her contributions have earned her numerous accolades, including the National Science Fund for Excellent Young Scholars (2016), Tan Jiazhen Life Science Innovation Award (2020), Tencent Xplorer Prize (2021), and New Cornerstone Investigator (2022). She actively contributes to the scientific community as an Editor for eLife and a committee member of the Chinese Society for Stem Cell Biology, where she helps shape research directions and foster interdisciplinary collaboration.
Pancreatic β cells are the sole producers of insulin in humans and nearly all other vertebrates. However, generating functional β cells in vitro has proven to be a challenging task. Our recent study identified a Procr+ cell population within adult mouse pancreatic islets. These cells lack differentiation markers and exhibit characteristics of epithelial-to-mesenchymal transition (EMT). Through genetic lineage tracing, we discovered that Procr islet cells undergo clonal expansion and generate all four endocrine cell types during adult homeostasis. When isolated, Procr cells, which comprise approximately 1% of islet cells, can form islet-like organoids when cultured at clonal density. These organoids can be exponentially expanded over extended periods through serial passaging, with differentiation inducible at any point in the culture. The differentiated islet organoids consist of all endocrine cell types of the islet and are glucose-responsive for insulin secretion. When transplanted into diabetic mice, the islet organoids effectively restore normoglycemia. Our findings demonstrate the presence of a population of resident stem/progenitor cells within the adult pancreatic islet. We will also further discuss the relevance of these progenitors in islet development and their potential to stimulate islet regeneration.
BIO
Yi Arial Zeng is a Principal Investigator at the Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences. She obtained her Ph.D. from Simon Fraser University in Canada and completed her postdoctoral training at Stanford University. Her research focuses on understanding the regulatory mechanisms of adult stem cells across various tissues and their interactions with the surrounding niche. She has concentrated her efforts on Procr (protein C receptor), a target of Wnt and Yap signaling pathways, which has been identified as a surface marker for adult stem cells in multiple tissues, including the mammary gland, blood vessel endothelium, hematopoietic system, and ovarian epithelium. Her recent work uncovers a unique pancreatic islet resident stem/progenitor cell population in adult mouse and establishes a method to expand these cells and differentiate them in vitro into functional islet organoids. This research lays the groundwork for exploring islet regeneration in situ and exploited for the expansion and induction of functional β cells in vitro for the treatment of diabetes. Her contributions have earned her numerous accolades, including the National Science Fund for Excellent Young Scholars (2016), Tan Jiazhen Life Science Innovation Award (2020), Tencent Xplorer Prize (2021), and New Cornerstone Investigator (2022). She actively contributes to the scientific community as an Editor for eLife and a committee member of the Chinese Society for Stem Cell Biology, where she helps shape research directions and foster interdisciplinary collaboration.
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Adrian TEO
Institute of Molecular and Cell Biology, A*STAR, Singapore "Functionalising genes associated with pancreatic beta cell dysfunction and diabetes" Pubmed |
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ABSTRACT
Diabetes is a debilitating chronic disease that is spiralling out of control, affecting nearly 600 million people worldwide. Fundamentally, the progressive failure of pancreatic beta cells results in decreased insulin secretion, ultimately giving rise to hyperglycaemia and overt diabetes. In the past decade, donor- and patient-derived human induced pluripotent stem cells (hiPSCs) coupled with an ability to differentiate them into pancreatic islet-like organoids in fully-suspension cultures now provide an invaluable opportunity to study human beta cell failure in vitro. We have been contributing to the field by generating hiPSCs from monogenic and type 2 diabetes donors, followed by comprehensive diabetes disease modelling. Here, I will highlight our decade of efforts in using diabetes patient-specific hiPSC-derived pancreatic islet-like organoids harbouring defined gene mutations or variants to study human diabetes disease mechanisms, including that of monogenic diabetes and type 2 diabetes.
BIO
Adrian Teo obtained his B.Sc. (1st Class) from the National University of Singapore (NUS). He completed his Ph.D. on stem cell biology with Prof Ludovic Vallier at the University of Cambridge, under an A*STAR Scholarship. Concurrently, he was also an Honorary Cambridge Commonwealth Trust Scholar. He then trained with Prof Rohit Kulkarni at Joslin Diabetes Center, Harvard Medical School, as a Juvenile Diabetes Research Foundation (JDRF) fellow, on pancreatic islet biology and diabetes. Adrian is currently a Senior Principal Investigator and an Assoc. Prof. at the Institute of Molecular and Cell Biology (IMCB), A*STAR; Division Director of the Cell and Molecular Therapy (CMT) Division at IMCB, A*STAR; a tenured Associate Professor at Yong Loo Lin School of Medicine, National University of Singapore; and Director of Graduate Affairs (DGA) of the Biomedical Research Council (BMRC), A*STAR. His laboratory uses human pluripotent stem cells for disease modelling of diabetes, developing therapeutics and cell therapy. He is also a co-founder of BetaLife Pte Ltd focused on the use of stem cell therapy for diabetes patients. He is a member of the Oxbridge Society of Singapore, the International Society for Stem Cell Research (ISSCR) and an EXCO member/Vice-Secretary of the Stem Cell Society Singapore (SCSS).
Diabetes is a debilitating chronic disease that is spiralling out of control, affecting nearly 600 million people worldwide. Fundamentally, the progressive failure of pancreatic beta cells results in decreased insulin secretion, ultimately giving rise to hyperglycaemia and overt diabetes. In the past decade, donor- and patient-derived human induced pluripotent stem cells (hiPSCs) coupled with an ability to differentiate them into pancreatic islet-like organoids in fully-suspension cultures now provide an invaluable opportunity to study human beta cell failure in vitro. We have been contributing to the field by generating hiPSCs from monogenic and type 2 diabetes donors, followed by comprehensive diabetes disease modelling. Here, I will highlight our decade of efforts in using diabetes patient-specific hiPSC-derived pancreatic islet-like organoids harbouring defined gene mutations or variants to study human diabetes disease mechanisms, including that of monogenic diabetes and type 2 diabetes.
BIO
Adrian Teo obtained his B.Sc. (1st Class) from the National University of Singapore (NUS). He completed his Ph.D. on stem cell biology with Prof Ludovic Vallier at the University of Cambridge, under an A*STAR Scholarship. Concurrently, he was also an Honorary Cambridge Commonwealth Trust Scholar. He then trained with Prof Rohit Kulkarni at Joslin Diabetes Center, Harvard Medical School, as a Juvenile Diabetes Research Foundation (JDRF) fellow, on pancreatic islet biology and diabetes. Adrian is currently a Senior Principal Investigator and an Assoc. Prof. at the Institute of Molecular and Cell Biology (IMCB), A*STAR; Division Director of the Cell and Molecular Therapy (CMT) Division at IMCB, A*STAR; a tenured Associate Professor at Yong Loo Lin School of Medicine, National University of Singapore; and Director of Graduate Affairs (DGA) of the Biomedical Research Council (BMRC), A*STAR. His laboratory uses human pluripotent stem cells for disease modelling of diabetes, developing therapeutics and cell therapy. He is also a co-founder of BetaLife Pte Ltd focused on the use of stem cell therapy for diabetes patients. He is a member of the Oxbridge Society of Singapore, the International Society for Stem Cell Research (ISSCR) and an EXCO member/Vice-Secretary of the Stem Cell Society Singapore (SCSS).