Nfe2 is dispensable for early but required for adult thrombocyte formation and function in zebrafish.

Nfe2 is dispensable for early but required for adult thrombocyte formation and function in zebrafish. Blood Adv. 2018 Dec 11;2(23):3418-3427 Authors: Rost MS, Shestopalov I, Liu Y, Vo AH, Richter CE, Emly SM, Barrett FG, Stachura DL, Holinstat M, Zon LI, Shavit JA Abstract The NFE2 transcription factor is expressed in multiple hematopoietic lineages with a well-defined role in regulating megakaryocyte biogenesis and platelet production in mammals. Mice deficient in NFE2 develop severe thrombocytopenia with lethality resulting from neonatal hemorrhage. Recent data in mammals reveal potential differences in embryonic and adult thrombopoiesis. Multiple studies in zebrafish have revealed mechanistic insights into hematopoiesis, although thrombopoiesis has been less studied. Rather than platelets, zebrafish possess thrombocytes, which are nucleated cells with similar functional properties. Using transcription activator-like effector nucleases to generate mutations in nfe2, we show that unlike mammals, zebrafish survive to adulthood in the absence of Nfe2. Despite developing severe thrombocytopenia, homozygous mutants do not display overt hemorrhage or reduced survival. Surprisingly, quantification of circulating thrombocytes in mutant 6-day-old larvae revealed no significant differences from wild-type siblings. Both wild-type and nfe2 null larvae formed thrombocyte-rich clots in response to endothelial injury. In addition, ex vivo thrombo...
Source: Adv Data - Category: Epidemiology Authors: Tags: Blood Adv Source Type: research