miR-21 promotes the differentiation of hair follicle-derived neural crest stem cells into Schwann cells

Abstract

Hair follicle-derived neural crest stem cells can be induced to differentiate into Schwann cells in vivo and in vitro. However, the underlying regulatory mechanism during cell differentiation remains poorly understood. This study isolated neural crest stem cells from human hair follicles and induced them to differentiate into Schwann cells. Quantitative RT-PCR showed that microRNA (miR)-21 expression was gradually increased during the differentiation of neural crest stem cells into Schwann cells. After transfection with the miR-21 agonist (agomir-21), the differentiation capacity of neural crest stem cells was enhanced. By contrast, after transfection with the miR-21 antagonist (antagomir-21), the differentiation capacity was attenuated. Further study results showed that SOX-2 was an effective target of miR-21. Without compromising SOX2 mRNA expression, miR-21 can down-regulate SOX protein expression by binding to the 3′-UTR of miR-21 mRNA. Knocking out the SOX2 gene from the neural crest stem cells significantly reversed the antagomir-21 inhibition of neural crest stem cells differentiating into Schwann cells. The results suggest that miR-21 expression was increased during the differentiation of neural crest stem cells into Schwann cells and miR-21 promoted the differentiation through down-regulating SOX protein expression by binding to the 3′-UTR of SOX2 mRNA.

mir-21 Overexpressing Mesenchymal Stem Cells Accelerate Fracture Healing in a Rat Closed Femur Fracture Model

“…Therefore, we detected the expression level of mir-21 and SOX-2 three days after osteogenic induction by q-PCR; the result proved our prediction that SOX-2 could be an effective target of mir-21. In addition, recent researches have confirmed our prediction that mir-21 can downregulate SOX-2 protein expression by binding to the 3′-UTR of it [ 41 , 42 ], which may partly explain how mir-21 exerts its biological function in vitro and in vivo .…”

REST–miR-21–SOX2 axis maintains pluripotency in E14Tg2a.4 embryonic stem cells

“…The suppressive effect of miR-21 has been recently seen in other cell types (Trohatou et al, 2014; Ni et al, 2014). Because pluripotency is a critical decision-making step for mESCs, one would expect that several counteracting mechanisms would modulate it so that the mESC pluripotency is maintained in equilibrium with environmental cues.…”

Changes in the Coding and Non-coding Transcriptome and DNA Methylome that Define the Schwann Cell Repair Phenotype after Nerve Injury

“…One of the most significantly regulated miRNAs, miR-21, has been shown to be a direct target of C-JUN in vascular endothelial cells ( Zhou et al., 2011 ), and we found that miR-21-3p is expressed at much lower levels in c-Jun -null injured nerves than in control injured nerves. The function of miR-21 in Schwann cells is unknown, but it has been shown to target Sox2 during differentiation of hair-follicle-derived neural crest stem cells into Schwann cells ( Ni et al., 2014 ).…”