Open AccessA comprehensive analysis of GATA-1-regulated miRNAs reveals miR-23a to be a positive modulator of erythropoiesis
Author(s) -
Yong Zhu,
Dongsheng Wang,
Fang Wang,
Tingting Li,
Lei Dong,
Huiwen Liu,
Yupo Ma,
Fengbing Jiang,
Hang Yin,
Wei Yan,
Min Luo,
Tang Zhong,
Jianan Zhang,
Qiang Wang,
Ruoyu Zhang,
Jingguo Zhou,
Jia Yu
Publication year - 2013
Publication title -
nucleic acids research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.008
H-Index - 537
eISSN - 1362-4954
pISSN - 0305-1048
DOI - 10.1093/nar/gkt093
Subject(s) - erythropoiesis , biology , microrna , microbiology and biotechnology , haematopoiesis , regulator , zebrafish , protein tyrosine phosphatase , downregulation and upregulation , cellular differentiation , stem cell , signal transduction , genetics , medicine , gene , anemia
miRNAs play important roles in many biological processes, including erythropoiesis. Although several miRNAs regulate erythroid differentiation, how the key erythroid regulator, GATA-1, directly orchestrates differentiation through miRNA pathways remains unclear. In this study, we identified miR-23a as a key regulator of erythropoiesis, which was upregulated both during erythroid differentiation and in GATA-1 gain-of-function experiments, as determined by miRNA expression profile analysis. In primary human CD34+ hematopoietic progenitor cells, miR-23a increased in a GATA-1-dependent manner during erythroid differentiation. Gain- or loss-of-function analysis of miR-23a in mice or zebrafish demonstrated that it was essential for normal morphology in terminally differentiated erythroid cells. Furthermore, a protein tyrosine phosphatase, SHP2, was identified as a downstream target of miR-23a that mediated its regulation of erythropoiesis. Taken together, our data identify a key GATA-1-miRNA axis in erythroid differentiation.