title: Knowledge Gaps in Rodent Pancreas Biology: Taking Human Pluripotent Stem Cell-Derived Pancreatic Beta Cells into Our Own Hands.
abstract: In the field of stem cell biology and diabetes, we and others seek to derive mature and functional human pancreatic β cells for disease modeling and cell replacement therapy. Traditionally, knowledge gathered from rodents is extended to human pancreas developmental biology research involving human pluripotent stem cells (hPSCs). While much has been learnt from rodent pancreas biology in the early steps toward Pdx1(+) pancreatic progenitors, much less is known about the transition toward Ngn3(+) pancreatic endocrine progenitors. Essentially, the later steps of pancreatic β cell development and maturation remain elusive to date. As a result, the most recent advances in the stem cell and diabetes field have relied upon combinatorial testing of numerous growth factors and chemical compounds in an arbitrary trial-and-error fashion to derive mature and functional human pancreatic β cells from hPSCs. Although this hit-or-miss approach appears to have made some headway in maturing human pancreatic β cells in vitro, its underlying biology is vaguely understood. Therefore, in this mini-review, we discuss some of these late-stage signaling pathways that are involved in human pancreatic β cell differentiation and highlight our current understanding of their relevance in rodent pancreas biology. Our efforts here unravel several novel signaling pathways that can be further studied to shed light on unexplored aspects of rodent pancreas biology. New investigations into these signaling pathways are expected to advance our knowledge in human pancreas developmental biology and to aid in the translation of stem cell biology in the context of diabetes treatments.
authors.affiliation: Stem Cells and Diabetes Laboratory, Discovery Research Division, Institute of Molecular and Cell Biology, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Munirah Mohamad
authors.initials: MM
authors.lastname: Santosa
authors.affiliation: Stem Cells and Diabetes Laboratory, Discovery Research Division, Institute of Molecular and Cell Biology , Singapore.
authors.forename: Blaise Su Jun
authors.initials: BS
authors.lastname: Low
authors.affiliation: Stem Cells and Diabetes Laboratory, Discovery Research Division, Institute of Molecular and Cell Biology, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Nicole Min Qian
authors.initials: NM
authors.lastname: Pek
authors.affiliation: Stem Cells and Diabetes Laboratory, Discovery Research Division, Institute of Molecular and Cell Biology, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
authors.forename: Adrian Kee Keong
authors.initials: AK
authors.lastname: Teo
keywords: beta cell; human; islet; pancreas; pluripotent stem cell
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