Mapping histologic and functional maturation of human endocrine pancreas across early postnatal periods
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.
Authors
- Nike Izmaylov (ORCID: https://orcid.org/0000-0001-5421-9030)
- Brandon A. Sherrod (ORCID: https://orcid.org/0000-0001-9433-7955)
- Kristie Aamodt (ORCID: https://orcid.org/0000-0003-0065-0786)
- Amanda L. Posgai (ORCID: https://orcid.org/0000-0002-9491-0958)
- Shaojun Mei (ORCID: https://orcid.org/0000-0003-4695-876X)
- Ke Xu (ORCID: https://orcid.org/0000-0002-6153-5055)
- Fan Feng (ORCID: https://orcid.org/0000-0002-5990-312X)
- Dale L. Greiner (ORCID: https://orcid.org/0000-0002-5923-339X)
- Hakmook Kang (ORCID: https://orcid.org/0000-0001-6876-4021)
- Yasminye D. Pettway (ORCID: https://orcid.org/0000-0001-6660-3013)
- Christopher V.E. Wright (ORCID: https://orcid.org/0000-0002-9260-4009)
- Rachana Haliyur (ORCID: https://orcid.org/0000-0002-3916-4286)
- Fong Cheng Pan (ORCID: https://orcid.org/0000-0002-9393-6574)
- Alexander L. Hopkirk (ORCID: https://orcid.org/0000-0002-1194-4221)
- Irina Kusmartseva (ORCID: https://orcid.org/0000-0003-2614-0813)
- Alvin C. Powers (ORCID: https://orcid.org/0000-0003-1941-5786)
- Marcela Briššová (ORCID: https://orcid.org/0000-0002-4999-3280)
- Rita Bottino (ORCID: https://orcid.org/0000-0003-1540-2996)
- Greg Poffenberger (ORCID: https://orcid.org/0000-0002-7363-4683)
- Mark A. Atkinson (ORCID: https://orcid.org/0000-0001-8489-4782)
- Jeeyeon Cha (ORCID: https://orcid.org/0000-0002-0312-2391)
- Diane C. Saunders (ORCID: https://orcid.org/0000-0002-8849-6746)
- Heather Durai
- Mingder Yang (ORCID: https://orcid.org/0000-0003-1986-0433)
- Maria Beery (ORCID: https://orcid.org/0000-0002-5326-3942)
- Radhika Aramandla
- Jeff Duryea
- NONGYAO NONPANYA
- KAI S. LEE
- Conrad V. Reihsmann
- Leonard D. Shultz
- Corey Davis
- Nathaniel Hart
- Keval P. Patel
- Alexandra Martin
Institutions
- Allegheny Health Network (US)
- University of Massachusetts Chan Medical School (US)
- Vanderbilt University (US)
- University of Florida (US)
- Allegheny-Singer Research Institute (US)
- VA Tennessee Valley Healthcare System (US)
- Jackson Laboratory (US)
- Vanderbilt Health (US)
- Vanderbilt University Medical Center (US)
- Florida College (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-06-29
- DOI
- https://doi.org/10.1038/s41467-026-73854-y
- Primary Topic
- Pancreatic function and diabetes
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Vanderbilt University
- Leona M. and Harry B. Helmsley Charitable Trust
- Human Islet Research Network
- National Institutes of Health