AI-guided analysis of human pancreatic islet sociology reveals distinct cell compositional changes in type 1 diabetes
Ward, C.; Banks-Tibbs, T.; Thorpe, H.; Giles, A. M.; Mabry, S. J.; Liu, J.-J.; Chang, H.-C.; Yang, J.; Carney, A. F.; Shaikh, H. M.; Woolley, L. M.; Joseph, P. N.; Kozel, J. D.; Rocha, E. M.; Rutter, G. A.; Tseng, G. C.; Liu, S.; Pless, L. L.; Freyberg, Z.
Show abstract
Human pancreatic islets exhibit greater anatomic and cellular heterogeneity than previously appreciated, raising fundamental questions about how their composition varies with age, sex, region, and islet size and how type 1 diabetes (T1D) alters these relationships. Yet these questions remained largely unresolved due to the bottleneck of manual tissue inspection. Here, we developed an integrated artificial intelligence (AI)-guided imaging, processing, and statistical pipeline enabling unbiased, high-throughput analysis of more than 2 million candidate islets from 106 non-diabetic (ND) and T1D donors. We identified age-, region-, sex-, and islet size-dependent differences in islet distribution and composition between ND and T1D donors. Profound {beta}-cell loss in T1D was accompanied by reciprocal -cell expansion, whereas {delta}-cells and pancreatic polypeptide cells were largely resilient. Cell area and pseudotime analyses uncovered regional and age-dependent trajectories of islet remodeling across T1D progression, along with distinct patterns of cytoarchitectural reorganization of the endocrine pancreas.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- An integrated map of cell type-specific gene expression in pancreatic islets 94%
- Microvascular homeostasis is compromised in pancreatic islets in a mouse model of beta cell loss and low-grade inflammation 94%
- Integrative proteogenomic analyses provide novel interpretations of type 1 diabetes risk loci through circulating proteins 94%
Similar papers in this journal
- Single-cell analysis of the human pancreas in type 2 diabetes using multi-spectral imaging mass cytometry 96%
- Chronic intermittent fasting impairs β-cell maturation and function in adolescent mice 95%
- Pericyte dysfunction and impaired vasomotion are hallmarks of islets during the pathogenesis of type 1 diabetes 95%
Similar papers in this journal
Similar papers in this journal
- Nerve-associated macrophages control adipose homeostasis across lifespan and restrain age-related inflammation 93%
- GDF3 promotes adipose tissue macrophage-mediated inflammation via altered chromatin accessibility during aging 92%
- Senescence-Induced Immune Remodeling Facilitates Metastatic Adrenal Cancer in a Sex-Dimorphic Manner 91%
Similar papers in this journal
- Islet vascularization is regulated by primary endothelial cilia via VEGF-A dependent signaling 95%
- Fluorescein-based sensors to purify human α-cells for functional and transcriptomic analyses 94%
- Coordination between ECM and cell-cell adhesion regulates the development of islet aggregation, architecture, and functional maturation 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.