Chronic inflammation directs an olfactory stem cell functional switch from neuroregeneration to immune defense (bulk RNA-Seq)

Although the olfactory mucosa possesses long-lived horizontal basal stem cells (HBCs) and remarkable regenerative capacity, the function of human olfactory neuroepithelium is significantly impaired in the setting of chronic rhinosinusitis. Here we used RNA sequencing to analyze the transcriptional profile of mouse HBCs in a chronic inflammatory milieu. Global gene expression analysis in inflamed HBCs reveals broad upregulation of NF-κB-regulated cytokines and chemokines accompanied by enhancement of “stemness”-related transcription factors. Our results provide evidence of basal stem cells as direct participants in the progression of chronic inflammation and identify a concomitant functional switch away from neuroregeneration. GFP+ HBCs from Krt17-EGFP; Cyp2g1-rtTA; TRE-TNF mice after 6 weeks of tissue-specific temporally-controlled olfactory inflammation were collected by FACS. GFP+ HBCs from Krt17-EGFP mice were isolated as normal control. The HBC mRNA transcriptional profile was analyzed by bulk RNA sequencing.