Dlk1-Mediated Temporal Regulation of Notch Signaling Is Required for Differentiation of Alveolar Type II to Type I Cells during Repair

• DOI: 10.1016/j.celrep.2019.02.046
• Publication Date: 2019-03-12T14:44:15Z
• Authors: Johanna Finn; Kilian Sottoriva; Kostandin V. Pajcini; Jan K. Kitajewski; Chang Chen; Wei Zhang; Asrar B. Malik; Yuru Liu
• Keywords: Male; 0301 basic medicine; 0303 health sciences; Receptors, Notch; QH301-705.5; Calcium-Binding Proteins; Cell Differentiation; Article; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Alveolar Epithelial Cells; Pneumonia, Bacterial; Animals; Regeneration; Female; Pseudomonas Infections; Biology (General); Cells, Cultured; Signal Transduction

Highlights•Notch signaling is activated in type II cells after Pseudomonas aeruginosa injury•After peak Notch activation, Dlk1 inhibits signaling•Dlk1 disruption impairs II-to-type I cell transition•Dlk1 inhibition of necessary for the repair alveolar injurySummaryLung (AT1) and (AT2) regulate structural integrity function alveoli. AT1, covering ∼95% surface area, are responsible gas exchange, whereas AT2 serve multiple functions, including through proliferation differentiation into AT1. However, mechanisms remain unclear. Here, we demonstrate, aeruginosa-induced acute lung injury mice, that non-canonical ligand (delta-like 1 homolog) essential AT2-to-AT1 differentiation. was at onset but later suppressed by Dlk1. Deletion induced persistent resulting stalled transition to AT1 accumulation an intermediate population expressed low levels both markers. Thus, expression leads precisely timed activates differentiation, leading repair.Graphical abstract