@article {120, title = {Genomic and physiological analyses of the zebrafish atrioventricular canal reveal molecular building blocks of the secondary pacemaker region.}, journal = {Cell Mol Life Sci}, volume = {78}, year = {2021}, month = {2021 Oct}, pages = {6669-6687}, abstract = {

The atrioventricular canal (AVC) is the site where key structures responsible for functional division between heart regions are established, most importantly, the atrioventricular (AV) conduction system and cardiac valves. To elucidate the mechanism underlying AVC development and function, we utilized transgenic zebrafish line sqet31Et expressing EGFP in the AVC to isolate this cell population and profile its transcriptome at 48 and 72 hpf. The zebrafish AVC transcriptome exhibits hallmarks of mammalian AV node, including the expression of genes implicated in its development and those encoding connexins forming low conductance gap junctions. Transcriptome analysis uncovered protein-coding and noncoding transcripts enriched in AVC, which have not been previously associated with this structure, as well as dynamic expression of epithelial-to-mesenchymal transition markers and components of TGF-β, Notch, and Wnt signaling pathways likely reflecting ongoing AVC and valve development. Using transgenic line Tg(myl7:mermaid) encoding voltage-sensitive fluorescent protein, we show that abolishing the pacemaker-containing sinoatrial ring (SAR) through Isl1 loss of function resulted in spontaneous activation in the AVC region, suggesting that it possesses inherent automaticity although insufficient to replace the SAR. The SAR and AVC transcriptomes express partially overlapping species of ion channels and gap junction proteins, reflecting their distinct roles. Besides identifying conserved aspects between zebrafish and mammalian conduction systems, our results established molecular hallmarks of the developing AVC which underlies its role in structural and electrophysiological separation between heart chambers. This data constitutes a valuable resource for studying AVC development and function, and identification of novel candidate genes implicated in these processes.

}, keywords = {Animals, Animals, Genetically Modified, Embryo, Nonmammalian, Gene Expression Regulation, Developmental, Genome, Genomics, Heart Septal Defects, Heart Valves, Myocardium, Organogenesis, Pacemaker, Artificial, Wnt Signaling Pathway, Zebrafish, Zebrafish Proteins}, issn = {1420-9071}, doi = {10.1007/s00018-021-03939-y}, author = {Abu Nahia, Karim and Migda{\l}, Maciej and Quinn, T Alexander and Poon, Kar-Lai and {\L}api{\'n}ski, Maciej and Sulej, Agata and Liu, Jiandong and Mondal, Shamba S and Pawlak, Micha{\l} and Bugajski, {\L}ukasz and Piwocka, Katarzyna and Brand, Thomas and Kohl, Peter and Korzh, Vladimir 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}} }