@article {124, title = {Adar-mediated A-to-I editing is required for embryonic patterning and innate immune response regulation in zebrafish.}, journal = {Nat Commun}, volume = {13}, year = {2022}, month = {2022 Sep 20}, pages = {5520}, abstract = {

Adenosine deaminases (ADARs) catalyze the deamination of adenosine to inosine, also known as A-to-I editing, in RNA. Although A-to-I editing occurs widely across animals and is well studied, new biological roles are still being discovered. Here, we study the role of A-to-I editing in early zebrafish development. We demonstrate that Adar, the zebrafish orthologue of mammalian ADAR1, is essential for establishing the antero-posterior and dorso-ventral axes and patterning. Genome-wide editing discovery reveals pervasive editing in maternal and the earliest zygotic transcripts, the majority of which occurred in the 3{\textquoteright}-UTR. Interestingly, transcripts implicated in gastrulation as well as dorso-ventral and antero-posterior patterning are found to contain multiple editing sites. Adar knockdown or overexpression affect gene expression by 12 hpf. Analysis of adar-/- zygotic mutants further reveals that the previously described role of Adar in mammals in regulating the innate immune response is conserved in zebrafish. Our study therefore establishes distinct maternal and zygotic functions of RNA editing by Adar in embryonic patterning along the zebrafish antero-posterior and dorso-ventral axes, and in the regulation of the\ innate immune response, respectively.

}, keywords = {Adenosine, Animals, Immunity, Innate, Inosine, Mammals, RNA, RNA-Binding Proteins, Zebrafish}, issn = {2041-1723}, doi = {10.1038/s41467-022-33260-6}, author = {Niescierowicz, Katarzyna and Pryszcz, Leszek and Navarrete, Cristina and Tralle, Eugeniusz and Sulej, Agata and Abu Nahia, Karim and Kasprzyk, Marta El{\.z}bieta and Misztal, Katarzyna and Pateria, Abhishek and Paku{\l}a, Adrianna and Bochtler, Matthias and Winata, Cecilia} } @article {122, title = {Multi-omics analyses of early liver injury reveals cell-type-specific transcriptional and epigenomic shift.}, journal = {BMC Genomics}, volume = {22}, year = {2021}, month = {2021 Dec 18}, pages = {904}, abstract = {

BACKGROUND: Liver fibrosis is a wound-healing response to tissue injury and inflammation hallmarked by the extracellular matrix (ECM) protein deposition in the liver parenchyma and tissue remodelling. Different cell types of the liver are known to play distinct roles in liver injury response. Hepatocytes and liver endothelial cells receive molecular signals indicating tissue injury and activate hepatic stellate cells which produce ECM proteins upon their activation. Despite the growing knowledge on the molecular mechanism underlying hepatic fibrosis in general, the cell-type-specific gene regulatory network associated with the initial response to hepatotoxic injury is still poorly characterized.

RESULTS: In this study, we used thioacetamide (TAA) to induce hepatic injury in adult zebrafish. We isolated three major liver cell types - hepatocytes, endothelial cells and hepatic stellate cells - and identified cell-type-specific chromatin accessibility and transcriptional changes in an early stage of liver injury. We found that TAA induced transcriptional shifts in all three cell types hallmarked by significant alterations in the expression of genes related to fatty acid and carbohydrate metabolism, as well as immune response-associated and vascular-specific genes. Interestingly, liver endothelial cells exhibit the most pronounced response to liver injury at the transcriptome and chromatin level, hallmarked by the loss of their angiogenic phenotype.

CONCLUSION: Our results uncovered cell-type-specific transcriptome and epigenome responses to early stage liver injury, which provide valuable insights into understanding the molecular mechanism implicated in the early response of the liver to pro-fibrotic signals.

}, keywords = {Animals, Endothelial Cells, Epigenomics, Liver, Zebrafish}, issn = {1471-2164}, doi = {10.1186/s12864-021-08173-1}, author = {Migda{\l}, Maciej and Tralle, Eugeniusz and Nahia, Karim Abu and Bugajski, {\L}ukasz and K{\k e}dzierska, Katarzyna Zofia and Garbicz, Filip and Piwocka, Katarzyna and Winata, Cecilia Lanny and Pawlak, Micha{\l}} }