Retinoic acid-induced upregulation of miR-219 promotes the differentiation of embryonic stem cells into neural cells

Haibo Wu; Jiamin Zhao; Beibei Fu; Songna Yin; Chao Song; Jingcheng Zhang; Shanting Zhao; Yong Zhang

doi:10.1038/cddis.2017.336

Retinoic acid-induced upregulation of miR-219 promotes the differentiation of embryonic stem cells into neural cells

Cell Death Dis. 2017 Jul 27;8(7):e2953. doi: 10.1038/cddis.2017.336.

Authors

Haibo Wu^{1

2}, Jiamin Zhao^{1

2}, Beibei Fu^{1

2}, Songna Yin², Chao Song^{1

2}, Jingcheng Zhang^{1

2}, Shanting Zhao¹, Yong Zhang^{1

2}

Affiliations

¹ College of Veterinary Medicine, Northwest A&F University, 22 Xinong Road, Yangling 712100, China.
² Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, 3 Taicheng Road, Yangling 712100, China.

Abstract

MicroRNAs (miRNAs) regulate critical cell processes, such as apoptosis, proliferation, and development. However, the role of miRNAs in embryonic stem cell (ESC) neural differentiation induced by retinoic acid (RA) and factors that govern neural directional differentiation remain poorly understood. In this study, we demonstrated that miR-219 is sufficient in promoting mouse ESCs to undergo neural differentiation. We discovered that Foxj3 and Zbtb18, two target genes of miR-219, are not able to determine the process of RA-induced differentiation, however they prevent ESCs from differentiating into neural cells. We identified four downstream genes, namely, Olig1, Zic5, Erbb2, and Olig2, which are essential to the gene interaction networks for neural differentiation. These data explain the mechanism of RA-induced neural differentiation of mESCs on the basis of miRNAs and support the crucial role of miR-219 in neurodevelopment.

MeSH terms

Animals
Basic Helix-Loop-Helix Transcription Factors / genetics
Basic Helix-Loop-Helix Transcription Factors / metabolism
Blotting, Western
Carrier Proteins / genetics
Carrier Proteins / metabolism
Cell Differentiation / drug effects
Cell Differentiation / genetics
Cell Line
DNA-Binding Proteins
Embryonic Stem Cells / cytology*
Embryonic Stem Cells / drug effects
Embryonic Stem Cells / metabolism
Female
Immunohistochemistry
Mice
Mice, Nude
MicroRNAs / genetics
MicroRNAs / metabolism*
Neurons / cytology
Neurons / drug effects
Neurons / metabolism*
Oligodendrocyte Transcription Factor 2 / genetics
Oligodendrocyte Transcription Factor 2 / metabolism
Receptor, ErbB-2 / genetics
Receptor, ErbB-2 / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factors
Tretinoin / pharmacology*

Substances

Basic Helix-Loop-Helix Transcription Factors
Carrier Proteins
DNA-Binding Proteins
MIRN219 microRNA, mouse
MicroRNAs
Olig1 protein, mouse
Olig2 protein, mouse
Oligodendrocyte Transcription Factor 2
Transcription Factors
Zic5 protein, mouse
Tretinoin
Erbb2 protein, mouse
Receptor, ErbB-2