Biology subjects

Beers, J.

Publications and source records attributed to Beers, J..

4 recordsLinked to original sources

bioRxiv2026

Systemic Analysis of Patient Derived Esophageal Epithelial Organoid Model Reveals Cell State Heterogeneity and Conservation of Differentiation Hierarchy

Background and Aims: Eosinophilic esophagitis (EoE) features prominent epithelial dysregulation that persists despite resolution of eosinophilia. Interleukin-13 (IL-13) is known to be a key upstream driver of epithelial abnormalities in EoE. We sought to benchmark an IL-13 esophageal organoid model against the in vivo epithelial state in EoE at a single cell resolution, to define in the role of IL-13 in aberrant epithelial development and inflammation in EoE, and to validate the IL-13 organoid as a model system to study the epithelial changes seen in EoE. Methods: We performed scRNA-Seq on esophageal biopsies from control and EoE patients, and esophageal biopsy-derived organoids with or without IL-13. We compared cellular composition, differentiation trajectories, pathway enrichment, and differential gene expression within both systems, and assessed findings at a protein level. Results: Seven distinct epithelial cell clusters were identified and preserved in both biopsies and organoids. EoE biopsies demonstrated expansion of cycling cells, whereas IL-13-treated organoids showed shift in the composition of the suprabasal compartments. Pseudotime topology was preserved across tissues, with a shift away from terminal differentiation in both EoE biopsies and IL-13-treated organoids. IL-13 reproduced changes in the transcription of central EoE genes and the dysregulation of epithelial proliferation and differentiation pathways seen in EoE. There was broad activation of immune related pathways within both EoE biopsies and IL-13-treated organoids, however, biopsies additionally showed activation in several immune and extracellular matrix remodeling programs that IL-13 alone did not reproduce. Conclusion: IL-13-treated esophageal organoids replicate key epithelial features of EoE including dysregulated epithelial development, impaired cornification, and inflammatory signals, while preserving lineage architecture, providing a tractable platform for epithelial-targeted mechanistic and therapeutic studies.

cell biology↗

bioRxiv2026

T cell dysregulation and remodeling in pediatric obesity and weight loss

Obesity is a chronic inflammatory disease associated with immune dysregulation. However, alterations in adaptive immune function remain unclear, particularly in the setting of childhood obesity and weight loss. We defined peripheral T cell dysregulation in a cross-sectional cohort of pediatric participants across weight categories and in a longitudinal cohort of adolescents with severe obesity undergoing bariatric surgery. We found increased expression of activation markers (including PD-1 and CD69) in non-naive CD8+ T cells whereas non-naive CD4+ T cells were skewed towards Tfh, Th17, and mixed Th2/Th17 populations. Consistent with a hyperactive state, T cells had enhanced capacity for inflammatory cytokine production (including IFN-{gamma} and TNF-), along with enrichment of gene sets associated with cytokine signaling, cell proliferation, and cell death. Notably, these phenotypic, functional, and transcriptional alterations were not fully resolved after bariatric surgery, despite clinically meaningful weight loss. Together, these findings demonstrate that pediatric obesity leads to dysregulation of adaptive immune function with incomplete normalization after weight loss. SUMMARYThe impact of pediatric obesity on immune cell function is not well understood. This study demonstrates that both CD4+ and CD8+ T cells are dysregulated in children living with obesity and further identifies that this dysregulated state persists following clinically significant weight loss.

immunology↗

bioRxiv2024

Proton pump inhibitors modulate esophageal epithelial barrier function and crosstalk with eosinophils

BackgroundEosinophilic esophagitis (EoE) is a chronic allergic disease characterized by esophageal dysfunction, type-2 inflammation, and esophageal eosinophilic infiltrate. While proton pump inhibitor (PPI) therapy is commonly used for EoE management, the underlying mechanism of action remains unclear. MethodsAir-liquid interface culture of esophageal epithelial cells was employed to investigate the impact of the PPI omeprazole on barrier integrity in IL-13-treated cultures. Epithelial chemokine secretion was assessed following stimulation with IL-13 and omeprazole, and the migration of eosinophils from healthy human donors was evaluated using 3 {micro}m pore-sized transwells. A co-culture system of epithelial cells and eosinophils was employed to study chemokine secretion and eosinophil adhesion and activation markers. ResultsOmeprazole treatment in the IL-13-treated air-liquid interface (ALI) model resulted in 186 differentially expressed genes and restored barrier integrity compared to ALI treated with IL-13 alone. Omeprazole treatment reduced STAT6 phosphorylation, downregulated calpain 14, and upregulated desmoglein-1 in the IL-13-treated air-liquid interface samples. IL-13-induced upregulation of Eotaxin-3, CXCL10, and periostin, but this was downregulated by omeprazole. Further, the expression of CD11b, CD18, and CD69 was lower on eosinophils from omeprazole-treated epithelial-eosinophil co-cultures, which also had lower levels of eotaxin-3, CXCL10, CCL2, and CCL4. ConclusionOmeprazole reduced the effects of IL-13 in both the epithelial air-liquid interface model and eosinophil-epithelial co-cultures, reducing barrier dysfunction, chemokine expression, and upregulation of eosinophil adhesion markers.

immunology↗

bioRxiv2019

Robust generation of erythroid and multilineage hematopoietic progenitors from human iPSCs using a scalable monolayer culture system

One of the most promising objectives of clinical hematology is to derive engraftable autologous hematopoietic stem cells (HSCs) from human induced pluripotent stem cells (iPSCs). Progress in translating iPSC technologies to the clinic relies on the availability of scalable differentiation methodologies. In this study, human iPSCs were differentiated for 21 days using STEMdiff, a monolayer-based approach for hematopoietic differentiation of human iPSCs that requires no replating, co-culture or embryoid body formation. Both monolayer and suspension cells were functionally characterized throughout differentiation. In the supernatant fraction, an early transient population of primitive CD235a+ erythroid cells first emerged, followed by hematopoietic progenitors with multilineage differentiation activity in vitro but no long-term engraftment potential in vivo. In later stages of differentiation, a nearly exclusive production of definitive erythroid progenitors was observed. In the adherent monolayer, we identified a prevalent population of mesenchymal stromal cells and limited arterial vascular endothelium (VE), suggesting that the cellular constitution of the monolayer may be inadequate to support the generation of HSCs with durable repopulating potential. Quantitative modulation of WNT/{beta}-catenin and activin/nodal/TGF{beta} signaling pathways with CHIR/SB molecules during differentiation enhanced formation of arterial VE, definitive multilineage and erythroid progenitors, but was insufficient to orchestrate the generation of engrafting HSCs. Overall, STEMdiff provides a clinically-relevant and readily adaptable platform for the generation of erythroid and multilineage hematopoietic progenitors from human pluripotent stem cells.\n\nHighlightsO_LIRobust, scalable and clinically-relevant monolayer-based culture system for hematopoietic differentiation of human iPSCs.\nC_LIO_LISuccessive emergence of primitive erythroid cells, definitive multilineage HSPCs and erythroid progenitors in the culture supernatant.\nC_LIO_LIAbundant mesenchymal cells and limited arterial vascular endothelium in the culture monolayer.\nC_LIO_LICHIR/SB molecules increase arterial vascular endothelium formation, suppress primitive hematopoiesis and promote definitive multilineage and erythroid progenitors.\nC_LI

developmental biology↗