Cebp1 and Cebpß transcriptional axis controls eosinophilopoiesis in zebrafish.

Eosinophils are a group of granulocytes well known for their capacity to protect the host from parasites and regulate immune function. Diverse biological roles for eosinophils have been increasingly identified, but the developmental pattern and regulation of the eosinophil lineage remain largely unknown. Herein, we utilize the zebrafish model to analyze eosinophilic cell differentiation, distribution, and regulation. By identifying eslec as an eosinophil lineage-specific marker, we establish a Tg(eslec:eGFP) reporter line, which specifically labeled cells of the eosinophil lineage from early life through adulthood. Spatial-temporal analysis of eslec+ cells demonstrates their organ distribution from larval stage to adulthood. By single-cell RNA-Seq analysis, we decipher the eosinophil lineage cells from lineage-committed progenitors to mature eosinophils. Through further genetic analysis, we demonstrate the role of Cebp1 in balancing neutrophil and eosinophil lineages, and a Cebp1-Cebpß transcriptional axis that regulates the commitment and differentiation of the eosinophil lineage. Cross-species functional comparisons reveals that zebrafish Cebp1 is the functional orthologue of human C/EBPεP27 in suppressing eosinophilopoiesis. Our study characterizes eosinophil development in multiple dimensions including spatial-temporal patterns, expression profiles, and genetic regulators, providing for a better understanding of eosinophilopoiesis.

Loss of Ripk3 attenuated neutrophil accumulation in a lipopolysaccharide-induced zebrafish inflammatory model.

Neutrophils are important effector cells during inflammation, which play complex roles. Therefore, investigating the regulation of neutrophil accumulation during inflammation might provide targets for treating related diseases. In the present study, we generated a ripk3-deficient zebrafish line to study the roles of Ripk3 in neutrophil-related inflammation. The homeostatic hematopoiesis and cytokine expression of the ripk3-deficient larvae were unaltered. The ripk3-deficient larvae with caudal fin fold injury exhibited similar neutrophil enrichment with wild-type larvae, suggesting that Ripk3 is not essential for non-infectious inflammatory responses. When challenged with lipopolysaccharide (LPS), the ripk3-deficient larvae showed significantly less neutrophil accumulation in the injection site and differential expression of several key cytokines. Ripk3 inhibitors could also attenuate neutrophil accumulation in wild-type larvae, indicating that Ripk3 could serve as a candidate target for inflammation treatment. In summary, our study indicated that Ripk3 has an essential role in LPS-induced inflammatory responses. It was suggested that the ripk3-deficient zebrafish might be applied in developing infectious disease models, while Ripk3 also has potential as an inflammation-treatment target.

Telomere configuration influences the choice of telomere maintenance pathways.

Telomere maintenance is required for chromosome stability, and telomeres are typically replicated by the action of telomerase. In yeast cells that lack telomerase, telomeres are maintained by alternative type I and type II recombination mechanisms. Previous studies identified several proteins to control the choice between two types of recombinations. Here, we demonstrate that configuration of telomeres also plays a role to determine the fate of telomere replication in progeny. When diploid yeasts from mating equip with a specific type of telomeric structure in their genomes, they prefer to maintain this type of telomere replication in their descendants. While inherited telomere structure is easier to be utilized in progeny at the beginning stage, the telomeres in type I diploids can gradually switch to the type II cells in liquid culture. Importantly, the TLC1/tlc1 yeast cells develop type II survivors suggesting that haploid insufficiency of telomerase RNA component, which is similar to a type of dyskeratosis congenital in human. Altogether, our results suggest that both protein factors and substrate availability contribute to the choice among telomere replication pathways in yeast.