Spatial epigenomics reveals stromal niche-associated regulatory programs across pancreatic neuroendocrine tumor grades
Abstract
Non-functional pancreatic neuroendocrine tumors (NF-PanNETs) account for the majority of pancreatic neuroendocrine neoplasms and exhibit substantial clinical and biological heterogeneity, yet their epigenetic regulation and spatial architecture remain poorly understood. Here, we present an integrative analysis of NF-PanNETs across multiple tumor grades using single-nucleus advent of transposase-accessible chromatin using sequencing (snATAC-seq) and spatial ATAC-seq. snATAC-seq identified grade-associated chromatin accessibility programs characterized by distinct transcription factor activities, including HNF1A and FOXA2 in low-grade tumors, ETS family factors in intermediate-grade tumors, SNAI-associated regulatory programs in high-grade tumors, and CEBPB- and TOX-associated immune states. Spatial ATAC-seq revealed spatially coordinated tumor-stroma interactions, with stroma-proximal regions enriched for MYC/FOX-associated proliferative programs and distal regions exhibiting SNAI-enriched invasive programs. Together, our study provides a spatially resolved epigenomic atlas of NF-PanNETs across tumor grades, offering a resource for understanding epigenetic heterogeneity and generating hypotheses regarding regulatory programs and tumor-stroma interactions for future functional and clinical investigation.
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BibTeX
@article{wang2026spatial,
title = {{Spatial epigenomics reveals stromal niche-associated regulatory programs across pancreatic neuroendocrine tumor grades}},
author = {Dejiang Wang and Xiangjun Di and Fu Gao and Gaocai Li and Liyun Lin and Shujie He and Di Zhang and Junyi Xu and Yu Jin and Yuanxin Liang and Michael Cecchini and Jill Lacy and John Kunstman and Pamela Kunz and Jing Du and Yang Liu},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117953},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03336-5},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Spatial epigenomics reveals stromal niche-associated regulatory programs across pancreatic neuroendocrine tumor grades
AU - Dejiang Wang
AU - Xiangjun Di
AU - Fu Gao
AU - Gaocai Li
AU - Liyun Lin
AU - Shujie He
AU - Di Zhang
AU - Junyi Xu
AU - Yu Jin
AU - Yuanxin Liang
AU - Michael Cecchini
AU - Jill Lacy
AU - John Kunstman
AU - Pamela Kunz
AU - Jing Du
AU - Yang Liu
PY - 2026
DA - 2026/10/19
JO - iScience
DO - 10.1016/j.isci.2026.117953
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03336-5
AB - Non-functional pancreatic neuroendocrine tumors (NF-PanNETs) account for the majority of pancreatic neuroendocrine neoplasms and exhibit substantial clinical and biological heterogeneity, yet their epigenetic regulation and spatial architecture remain poorly understood. Here, we present an integrative analysis of NF-PanNETs across multiple tumor grades using single-nucleus advent of transposase-accessible chromatin using sequencing (snATAC-seq) and spatial ATAC-seq. snATAC-seq identified grade-associated chromatin accessibility programs characterized by distinct transcription factor activities, including HNF1A and FOXA2 in low-grade tumors, ETS family factors in intermediate-grade tumors, SNAI-associated regulatory programs in high-grade tumors, and CEBPB- and TOX-associated immune states. Spatial ATAC-seq revealed spatially coordinated tumor-stroma interactions, with stroma-proximal regions enriched for MYC/FOX-associated proliferative programs and distal regions exhibiting SNAI-enriched invasive programs. Together, our study provides a spatially resolved epigenomic atlas of NF-PanNETs across tumor grades, offering a resource for understanding epigenetic heterogeneity and generating hypotheses regarding regulatory programs and tumor-stroma interactions for future functional and clinical investigation.
SN - 2589-0042
ER -