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Jingbin Yan,Yanna Liu,Yuehua Zhang,Zhaorui Ren,Fanyi Zeng 한국분자세포생물학회 2023 Molecules and cells Vol.46 No.4
Down syndrome (DS) is the most common autosomal aneuploidy caused by trisomy of chromosome 21. Previous studies demonstrated that DS affected mitochondrial functions, which may be associated with the abnormal development of the nervous system in patients with DS. Runt-related transcription factor 1 (RUNX1) is an encoding gene located on chromosome 21. It has been reported that RUNX1 may affect cell apoptosis via the mitochondrial pathway. The present study investigated whether RUNX1 plays a critical role in mitochondrial dysfunction in DS and explored the mechanism by which RUNX1 affects mitochondrial functions. Expression of RUNX1 was detected in induced pluripotent stem cells of patients with DS (DS-iPSCs) and normal iPSCs (N-iPSCs), and the mitochondrial functions were investigated in the current study. Subsequently, RUNX1 was overexpressed in N-iPSCs and inhibited in DS-iPSCs. The mitochondrial functions were investigated thoroughly, including reactive oxygen species levels, mitochondrial membrane potential, ATP content, and lysosomal activity. Finally, RNA-sequencing was used to explore the global expression pattern. It was observed that the expression levels of RUNX1 in DS-iPSCs were significantly higher than those in normal controls. Impaired mitochondrial functions were observed in DS-iPSCs. Of note, overexpression of RUNX1 in N-iPSCs resulted in mitochondrial dysfunction, while inhibition of RUNX1 expression could improve the mitochondrial function in DS-iPSCs. Global gene expression analysis indicated that overexpression of RUNX1 may promote the induction of apoptosis in DS-iPSCs by activating the PI3K/Akt signaling pathway. The present findings indicate that abnormal expression of RUNX1 may play a critical role in mitochondrial dysfunction in DS-iPSCs.
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Shaomei Liu,Jiaxin Li,Yuan Wu,Yanna Ren,Qi Liu,Qiyao Wang,Xiangshan Zhou,Menghao Cai,Yuanxing Zhang 한국유전학회 2017 Genes & Genomics Vol.39 No.3
Aspergillus glaucus HB1-19 is a typical marinederived fungus preferring the dependence on sea water for its growth, asexual development and polyketides biosynthesis. Therein, salt stress greatly functions even in superior to light illumination, which is also a critical regulation signal for fungi. Here, comparative RNA-seq analysis of this strain was performed under conditions of saltstress ? dark (group A), non salt-stress ? dark (group B), salt-stress ? light (group C). The RNA-seq generated a total of 19,024 unigenes with an average length of 1415 bp. Differentially expressed genes were very similar between group A and group C but greatly differed between group A and group B, proving that salt stress functioned superior to light illumination globally. Salt stress highly enhanced primary metabolism and activated Ras and MAPK signaling pathways. There seems no direct interaction between asexual development and polyketides biosynthesis. Salt stress inhibited terpenoids biosynthesis but showed little influences on polyketide pathway as well as other secondary metabolism pathways. These findings provide a better understanding of marine fungi adapting to marine environment. Also, it indicates that the so-called ‘salt stress-induced’ may truly be a ‘metal ions-induced’ for biosynthesis of secondary metabolites in marine fungi.
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