The article discusses a study that investigates the origin of adult pancreatic β-cells, challenging the prevailing belief that stem cells are the primary source for β-cell regeneration. The research, conducted by Yuval Dor and colleagues at Harvard University, introduces a genetic lineage tracing method to determine whether β-cells arise from stem cells or from the self-duplication of existing β-cells. The study focuses on the postnatal origins of β-cells, which have been a subject of debate in the scientific community. The researchers developed a transgenic mouse model where β-cells are labeled with a tamoxifen-inducible Cre/lox system, allowing them to track the lineage of β-cells over time. By analyzing the presence of labeled β-cells after a "chase" period, they found that new β-cells are primarily derived from pre-existing β-cells rather than from stem cells. This conclusion is supported by the observation that the frequency of labeled β-cells remains constant over time, suggesting that β-cells maintain a significant proliferative capacity in vivo. The study also examines the formation of new islets and finds that no new islets are generated from stem cells during adult life. Instead, small clusters of β-cells are likely static mini-islets or remnants of older islets. Additionally, the researchers tested β-cell regeneration after partial pancreatectomy and found that new β-cells are also derived from existing β-cells, not from stem cells. These findings challenge the notion that adult stem cells play a significant role in β-cell replenishment and suggest that terminally differentiated β-cells retain the ability to self-duplicate. The study highlights the importance of direct lineage tracing methods in understanding cell origins and has implications for cell-based therapies for diabetes, emphasizing the potential of differentiated β-cells for therapeutic expansion.The article discusses a study that investigates the origin of adult pancreatic β-cells, challenging the prevailing belief that stem cells are the primary source for β-cell regeneration. The research, conducted by Yuval Dor and colleagues at Harvard University, introduces a genetic lineage tracing method to determine whether β-cells arise from stem cells or from the self-duplication of existing β-cells. The study focuses on the postnatal origins of β-cells, which have been a subject of debate in the scientific community. The researchers developed a transgenic mouse model where β-cells are labeled with a tamoxifen-inducible Cre/lox system, allowing them to track the lineage of β-cells over time. By analyzing the presence of labeled β-cells after a "chase" period, they found that new β-cells are primarily derived from pre-existing β-cells rather than from stem cells. This conclusion is supported by the observation that the frequency of labeled β-cells remains constant over time, suggesting that β-cells maintain a significant proliferative capacity in vivo. The study also examines the formation of new islets and finds that no new islets are generated from stem cells during adult life. Instead, small clusters of β-cells are likely static mini-islets or remnants of older islets. Additionally, the researchers tested β-cell regeneration after partial pancreatectomy and found that new β-cells are also derived from existing β-cells, not from stem cells. These findings challenge the notion that adult stem cells play a significant role in β-cell replenishment and suggest that terminally differentiated β-cells retain the ability to self-duplicate. The study highlights the importance of direct lineage tracing methods in understanding cell origins and has implications for cell-based therapies for diabetes, emphasizing the potential of differentiated β-cells for therapeutic expansion.