Suprabasal cells retaining stem cell identity programs drive basal cell hyperplasia in eosinophilic esophagitis.
Margarette H ClevengerAdam L KaramiDustin A CarlsonPeter J KahrilasNirmala GonsalvesJohn E PandolfinoDeborah R WinterKelly A WhelanMarie-Pier TétreaultPublished in: bioRxiv : the preprint server for biology (2023)
Eosinophilic esophagitis (EoE) is an esophageal immune-mediated disease characterized by eosinophilic inflammation and epithelial remodeling, including basal cell hyperplasia (BCH) and loss of differentiation. Although BCH correlates with disease severity and with persistent symptoms in patients in histological remission, the molecular processes driving BCH remain poorly defined. Here, we demonstrate that despite the presence of BCH in all EoE patients examined, no increase in basal cell proportion was observed by scRNA-seq. Instead, EoE patients exhibited a reduced pool of KRT15+ COL17A1+ quiescent cells, a modest increase in KI67+ dividing epibasal cells, a substantial increase in KRT13+ IVL+ suprabasal cells, and a loss of differentiated identity in superficial cells. Suprabasal and superficial cell populations demonstrated increased quiescent cell identity scoring in EoE with the enrichment of signaling pathways regulating pluripotency of stem cells. However, this was not paired with increased proliferation. Enrichment and trajectory analyses identified SOX2 and KLF5 as potential drivers of the increased quiescent identity and epithelial remodeling observed in EoE. Notably, these findings were not observed in GERD. Thus, our study demonstrates that BCH in EoE results from an expansion of non-proliferative cells that retain stem-like transcriptional programs while remaining committed to early differentiation.
Keyphrases
- induced apoptosis
- stem cells
- end stage renal disease
- cell cycle arrest
- single cell
- signaling pathway
- chronic kidney disease
- cell therapy
- ejection fraction
- oxidative stress
- newly diagnosed
- peritoneal dialysis
- endoplasmic reticulum stress
- transcription factor
- systemic lupus erythematosus
- rna seq
- physical activity
- cell death
- rheumatoid arthritis
- radiation therapy
- mesenchymal stem cells
- genome wide
- bone marrow
- cell proliferation
- lymph node
- patient reported
- neoadjuvant chemotherapy
- chronic rhinosinusitis
- disease activity