Cited4a limits cardiomyocyte dedifferentiation and proliferation during zebrafish heart regeneration.

Cardiac regeneration involves the interplay of complex interactions between many different cell types, including cardiomyocytes. The exact mechanism that enables cardiomyocytes to undergo dedifferentiation and proliferation to replace lost cells has been intensely studied. Here we report a single nuclear RNA sequencing profile of the injured zebrafish heart and identify distinct cardiomyocyte populations in the injured heart.

Amphiphilic shuttle peptide delivers base editor ribonucleoprotein to correct the CFTR R553X mutation in well-differentiated airway epithelial cells.

Base editing could correct nonsense mutations that cause cystic fibrosis (CF), but clinical development is limited by the lack of delivery methods that efficiently breach the barriers presented by airway epithelia. Here, we present a novel amphiphilic shuttle peptide based on the previously reported S10 peptide that substantially improved base editor ribonucleoprotein (RNP) delivery. Studies of the S10 secondary structure revealed that the alpha-helix formed by the endosomal leakage domain (ELD), but not the cell penetrating peptide (CPP), was functionally important for delivery.

IL-13 induces loss of CFTR in ionocytes and reduces airway epithelial fluid absorption.

The airway surface liquid (ASL) plays a crucial role in lung defense mechanisms, and its composition and volume are regulated by the airway epithelium. The cystic fibrosis transmembrane conductance regulator (CFTR) is abundantly expressed in a rare airway epithelial cell type called an ionocyte. Recently, we demonstrated that ionocytes can increase liquid absorption through apical CFTR and basolateral barttin/chloride channels, while airway secretory cells mediate liquid secretion through apical CFTR channels and basolateral NKCC1 transporters.

The pH-sensitive translocation of V-ATPase in the small airway of cystic fibrosis pigs.

In contrast to pig large airways, the pH of airway surface liquid (ASL) in pig small airways is regulated by CFTR-mediated HCO secretion and the vacuolar-type H ATPase (V-ATPase) proton secretion. We hypothesized that, in cystic fibrosis (CF), the ASL pH of small airways is acidic, and the V-ATPase is internalized. We quantified proton secretion during the addition of an alkaline test solution by measuring changes in a pH-dependent fluorescent dye generated by porcine small airway epithelia in the absence and presence of bafilomycin A1.