Tyrosyl-tRNA synthetase stimulates thrombopoietin-independent hematopoiesis accelerating recovery from thrombocytopenia.

ABSTRACT: New mechanisms behind blood cell formation continue to be uncovered, with therapeutic approaches for hematological diseases being of great interest. Here we report an enzyme in protein synthesis, known for cell-based activities beyond translation, is a factor inducing megakaryocyte-biased hematopoiesis, most likely under stress conditions. We show an activated form of tyrosyl-tRNA synthetase (YRS^ACT), prepared either by rationally designed mutagenesis or alternative splicing, induces expansion of a previously unrecognized high-ploidy Sca-1⁺ megakaryocyte population capable of accelerating platelet replenishment after depletion. Moreover, YRS^ACT targets monocytic cells to induce secretion of transacting cytokines that enhance megakaryocyte expansion stimulat

SUBMITTER: Kanaji T 

PROVIDER: S-EPMC6126720 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature