IBRIC -inStem study indicate acute Notch inhibition in mouse models uncovers distinctive Club Cells to repair lung airways
Regeneration and repair of the lungs and airways is crucial to recover from environmental insults like pollution, allergens and infections breathed in with air. Focusing on the tiniest of the lung airways – the terminal bronchioles in the lower airways – Dr Arjun Guha’s Lab investigated the stem cells called Club Cells (CCs) that reside in this tissue. CCs are facultative stem cells maintained by Notch signaling. If he Notch signaling is shut down, these facultative stem cells terminally differentiate into multicilliated cells of the lung airways, losing their pluripotency. Surprisingly, when Notch signaling was disrupted in mouse models, it was found that terminal bronchioles are niches for variant club cells (v-CCs) that have a different fate. These vCCs escape the negative effect of Notch inhibition by depending on Wnt signaling and thus take on a progenitor fate to regenerate the airway. This discovery serves as another step in understanding the cellular and molecular mechanisms that govern lung regeneration.
Lingamallu SM, Deshpande A, Joy N, et al. Neuroepithelial bodies and terminal bronchioles are niches for distinctive club cells that repair the airways following acute notch inhibition. Cell Reports. 2024;43(9). doi:10.1016/j.celrep.2024.114654
