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<p>Human endocrine cell differentiation and islet morphogenesis play critical roles in determining islet cell mass and function, but the events and timeline of these processes are incompletely defined. To better understand early human islet cell development and maturation, we collected 123 pediatric pancreata and mapped morphological and spatiotemporal changes from birth through the first ten years of life. Using quantitative analyses and a combination of complementary tissue imaging approaches, including confocal microscopy and whole-slide multiplex imaging, we developed an integrated model for endocrine cell formation and islet architecture, including endocrine cell type heterogeneity and abundance, endocrine cell proliferation, and islet vascularization and innervation. We also assessed insulin and glucagon secretory profiles in isolated islet preparations from pediatric donors aged 2 months to 10 years and found a temporal difference in the maturation of insulin secretion compared to glucagon secretion. This comprehensive summary of postnatal and pediatric pancreatic islet development provides a framework for future studies and for integrating emerging genetic and genomic data related to islet biology and diabetes risk.</p>

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Mapping histologic and functional maturation of human endocrine pancreas across early postnatal periods

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月29日

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  • Diane C. Saunders,
  • Fan Feng,
  • Alexander L. Hopkirk,
  • Kristie I. Aamodt,
  • Nathaniel Hart,
  • Fong Cheng Pan,
  • Conrad V. Reihsmann,
  • Nike Izmaylov,
  • Shaojun Mei,
  • Brandon A. Sherrod,
  • Corey Davis,
  • Nongyao Nonpanya,
  • Yasminye D. Pettway,
  • Keval P. Patel,
  • Kai S. Lee,
  • Jeff Duryea,
  • Rachana Haliyur,
  • Radhika Aramandla,
  • Heather Durai,
  • Greg Poffenberger,
  • Alexandra Martin,
  • Amanda L. Posgai,
  • Irina Kusmartseva,
  • Maria L. Beery,
  • Mingder Yang,
  • Ke Xu,
  • Hakmook Kang,
  • Dale L. Greiner,
  • Leonard D. Shultz,
  • Jean-Philippe Cartailler,
  • Rita Bottino,
  • Mark A. Atkinson,
  • Christopher V. E. Wright,
  • Alvin C. Powers,
  • Marcela Brissova

摘要

Human endocrine cell differentiation and islet morphogenesis play critical roles in determining islet cell mass and function, but the events and timeline of these processes are incompletely defined. To better understand early human islet cell development and maturation, we collected 123 pediatric pancreata and mapped morphological and spatiotemporal changes from birth through the first ten years of life. Using quantitative analyses and a combination of complementary tissue imaging approaches, including confocal microscopy and whole-slide multiplex imaging, we developed an integrated model for endocrine cell formation and islet architecture, including endocrine cell type heterogeneity and abundance, endocrine cell proliferation, and islet vascularization and innervation. We also assessed insulin and glucagon secretory profiles in isolated islet preparations from pediatric donors aged 2 months to 10 years and found a temporal difference in the maturation of insulin secretion compared to glucagon secretion. This comprehensive summary of postnatal and pediatric pancreatic islet development provides a framework for future studies and for integrating emerging genetic and genomic data related to islet biology and diabetes risk.