GSE168127 The NOTCH3 Downstream Target HEYL Regulates Human Airway Epithelial Club Cell Differentiation [scRNA-Seq]

Contributor : Matthew S WaltersSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensBasal cells (BC) are the resident stem/progenitor cells of the adult pseudostratified airway epithelium, whose differentiation program is orchestrated by the NOTCH signaling pathway. NOTCH3 receptor mediated signaling regulates BC to club cell differentiation; however, the downstream responses that regulate this process are largely unknown. In the present study we utilized an in vitro air-liquid interface model of the human pseudostratified airway epithelium to identify the NOTCH3-dependent downstream genes/pathways that regulate human BC to club cell differentiation. Activation of NOTCH3 signaling in BC via lentivirus-mediated over-expression of the active NOTCH3 intracellular domain (NICD3) promoted club cell differentiation. Bulk RNA-seq analysis of control vs NICD3 -transduced cells, identified 692 NICD3 responsive genes enriched for pathways linked to airway epithelial biology and differentiation including Wnt/ β-catenin Signaling. Expression of the classical NOTCH target HEYL increased in response to NOTCH3 activation and positively correlated with the club cell marker SCGB1A1. Further, using single-cell RNA-seq, we report that HEYL+ cells primarily clustered with SCGB1A1+ and NOTCH3+ cells. Moreover, HE YL protein co-localized with SCGB1A1 in ALI cultures in vitro and in the human and mouse airway epithelium in vivo. siRNA-mediated knockdown of HEYL in...

Source: GEO: Gene Expression Omnibus - March 4, 2021 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research