潘光锦,神经细胞 z-bo 2020-08-18 562

　　Pan Guangjin’s research group at the Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences studied the molecular regulatory mechanism of nerve cell fate determination and found that miR-376c, a member of the miRNA cluster miR-379-656 in human pluripotent stem cells, can promote The differentiation process of neural stem cells, while inhibiting miR-376c has the opposite effect.

　　The miR-379-656 cluster, located in the DLK-DIO3 region of the imprinted gene on chromosome 14 in the human genome, contains about 50 miRNAs and is highly conserved in mammals (mammal; mammalian). Its expression is mainly found in embryos And the brain, but its specific regulatory function is not clear. This study shows that miR-376c can target SMAD4 to inhibit the expression of SMAD4. SMAD4 factor is an important mediator in the TGF-β signaling pathway (Signaling Pathway), which can transduce extracellular TGF-β signals into the nucleus, and then play a role in regulating the expression of downstream genes of TGF-β signaling. TGF-β signal has been proved to play an important role in inhibiting neural development and differentiation, maintaining pluripotency of human pluripotent stem cells, and in the early induction of iPS cells. Further studies have shown that the TGF-β signaling pathway required in human pluripotent stem cell culture can activate SMAD4 as a transcription factor to bind to the upstream of the promoter of human neural stem cell marker gene PAX6 and the upstream of human miR-376c gene promoter. This inhibits the transcription of PAX6 and miR-376c genes.

　　"The above research results show that miR-376c and the TGF-β signaling pathway (Signaling Pathway) have a mutual antagonism, and jointly regulate the cell fate transition of human pluripotent stem cells from a pluripotent state to neural stem cell differentiation.

　　Mutual antagonistic regulation of miR-376c and TGF-β signaling pathway (Signaling Pathway) in the neural differentiation of human pluripotent stem cells