miRNA-7145-cuedc2 axis controls hematopoiesis through JAK1/STAT3 signaling pathway

Abstract

Hematopoiesis ensures oxygen diffusion, tissue remodeling and immune protection in vertebrate. During embryogenesis, hemangioblasts are the source of all blood cells. Gata1a and pu.1 are co-existed in hemangioblasts when hemangioblasts are not differentiated into blood cells. However, the genes that determine the differentiation of hemangioblasts into myeloid or erythroid have not been fully uncovered. Here we showed that miRNA-7145, a previously unknown function miRNA, was enriched in erythrocytes at definitive wave, but not expressed in myeloid cells. Gain-of-function and loss-of-function analysis of miRNA-7145 revealed that miRNA-7145 functions as a strong inhibitor for myeloid progenitor cells differentiation while commitment for primitive erythropoiesis. Furthermore, we confirmed that cuedc2 is one of miRNA-7145 targeted-genes. Indeed, over-expression or knock-down of cuedc2 partially rescues the phenotype caused by miRNA-7145 gain-of-function or loss-of-function. Meanwhile, Gain-of-function and loss-of-function analysis of cuedc2 showed that cuedc2 is required for myelopoiesis while against to erythropoiesis. Finally, we found that over-expression of zebrafish cuedc2 in 293T cell inhibits JAK1/STAT3 signaling pathway. Collectively, our results uncover a previously unknown miRNA-7145-cuedc2 axis, which regulate hematopoiesis through inhibiting JAK1/STAT3 signaling pathway.