Abstract
Embryonic stem cells (ESCs) are pluripotent cells and have the capability for differentiation into any of the three embryonic germ layers. The Wnt/β-Catenin pathway has been shown to play an essential role in ESC differentiation regulation. Activation of β-Catenin by post-translational modification has been extensively studied. However, mechanism(s) of post-transcriptional regulation of β-Catenin are not well defined. In this study, we report an RNA recognition motif-containing protein (RNA binding motif protein 46, RBM46) which regulates the degradation of β-Catenin mRNA. Our results show that Rbm46 is distributed primarily in the cytoplasm of mouse ESCs (mESCs) and is elevated during the process of ESC differentiation. In addition, overexpression of Rbm46 results in differentiation of mESCs into trophectoderm, while knock-down of Rbm46 leads to mESC differentiation into endoderm. β-Catenin, a key effector in the Wnt pathway which has been reported to play a significant role in the regulation of ESC differentiation, is post-transcriptionally regulated by Rbm46. Our study reveals Rbm46 plays a novel role in the regulation of ESC differentiation.
Highlights
Mouse Embryonic stem cells (ESCs) were first isolated from the inner cell masses of late blastocysts [1]
We evaluated expression levels of Rbm46 during Mouse ESCs (mESCs) differentiation. mESCs were induced to differentiate by removal of leukemia inhibitory factor (LIF) [14], and mRNA levels of Oct4 and Rbm46 were evaluated with qPCR
Our study reveals that Rbm46 is a critical regulator of ESC pluripotency based on changes observed in mESC differentiation under the influence of alterations in Rbm46
Summary
Mouse ESCs (mESCs) were first isolated from the inner cell masses of late blastocysts [1]. Stem cell differentiation is regulated by a complex network which includes certain critical transcription factors such as Nanog, SOX2, and OCT4 [3] These proteins form a mutual regulatory circuit, and coordinate their activity with other differentiation related transcription factors such as REST, SKIL and HESX1, and with some histone modifying complexes (for example SMARCAD1, MYST3 and SET) [4, 5] to regulate stem cell Differentiation. In addition to this primary regulatory circuit, some signaling pathways are involved in stem cell regulation [6, 7]. The Wnt signaling pathway has emerged as an PLOS ONE | DOI:10.1371/journal.pone.0172420 February 17, 2017
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