What does this research mean for the field?

During the first decade of life, the developing human pancreas possesses a distinct cellular and regulatory landscape in which macrophages constitute the most abundant immune cell population. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.ESTABLISHES_NEW_DIRECTION.

June 7, 2026

3109-LB: A Single-Cell Multiomic Atlas of the Developing Human Pancreas from the Neonatal Period through Childhood

Key Points

To generate a comprehensive single-cell transcriptomic and epigenomic atlas of the pediatric human pancreas during early life.
Acquired flash-frozen pancreatic tissues from 16 organ donors across neonatal, infancy, and childhood stages.
Optimized nuclei isolation protocol to enable multiplexing for single-cell RNA-seq and single-nucleus ATAC-seq.
Utilized randomized block design to minimize batch effects in the analysis.
scRNA-seq analysis identified 583,452 cells with a diverse distribution of pancreatic cell types across stages.
The most abundant immune cell population was macrophages, constituting 55.8% of cells.
snATAC-seq produced over 300,000 nuclei, mapping chromatin accessibility during the same developmental phases.

Abstract

Introduction and Objective: The first decade of life is critical for β cell mass establishment and maturation, coinciding with the onset of type 1 diabetes (T1D)-directed autoimmunity. Despite its significance, the cellular and regulatory landscape of the human pancreas after birth remains poorly understood, limiting our knowledge of the processes that promote islet endocrine cell expansion and maturation. The objective is to generate a comprehensive single-cell transcriptomic and epigenomic atlas of the pediatric human pancreas spanning neonatal, infancy, and childhood stages. Methods: Flash-frozen biobanked pancreatic tissues from 16 organ donors were acquired from three different postnatal stages: neonatal (birth to 3 months; n=4, 2F/2M), infancy (≥3 to 24 months; n=6, 3F/3F), and childhood (≥2 to ≤10 years; n=6, 3F/3M). We optimized a nuclei isolation protocol, validating its performance by microscopy and bulk-ATAC profiling. Using randomized block design to minimize batch effects, we multiplexed pancreatic samples for single-cell (sc) RNA-seq and single-nucleus (sn) ATAC-seq. Results: scRNA-seq of 16 pediatric donors yielded 583,452 cells, revealing a broad and representative distribution of pancreatic cell types across all developmental stages. Macrophages were the most abundant immune cell population (n=18,585; 55.8%) in the developing pancreas, a finding validated by immunocytochemistry and CO-Detection by indEXing (CODEX). In parallel, snATAC-seq generated 300,000 high-quality nuclei, providing a paired chromatin accessibility map across the same developmental window. Conclusion: This study developed a cost-effective multi-omic framework for profiling the developing human pancreas and created the first integrated transcriptomic and epigenomic atlas spanning neonatal through childhood stages. These data establish a foundation for exploring how genetic risk for T1D manifests in cellular and regulatory changes during early development and serve as a benchmark resource for the field. Disclosure S. Lin: None. A.K. Huber: None. H.T. Vu: None. P. Orchard: None. R. Jenkins: None. S. Mei: None. A. Coldren: None. D.C. Saunders: None. A.C. Powers: None. M. Brissova: None. S. Parker: Research Support; Current; Pfizer Inc. Consultant; Ended; Novo Nordisk. N. Nonpanya: None. O.M. Bernal-Assis: None. R. Bottino: None. Funding National Institutes of Health (U01DK135017, R01DK129469)

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