TBX3诱导人多能干细胞偏向分化为心脏起搏器样细胞

IF 1 4区 生物学 Q4 DEVELOPMENTAL BIOLOGY Gene Expression Patterns Pub Date : 2021-06-01 DOI:10.1016/j.gep.2021.119184
Ying Yan , Feng Liu , Xitong Dang , Rui Zhou , Bin Liao
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引用次数: 3

摘要

背景tbx3在胚胎心脏发育过程中窦房结(SAN)的形成中起关键作用。然而,TBX3在推动人类诱导多能干细胞(hiPSC)向起搏器细胞分化中的作用仍有待探索。结果采用人诱导多能干细胞(human induced pluripotent stem cells, hiPSC)的泛心肌细胞分化方案,在分化后第5天将TBX3基因导入分化中的hiPSC,并在第21天评估起搏器样心肌细胞的分化情况。结果显示,TBX3显著诱导hiPSC偏向分化为起搏样细胞,显著增加san特异性标记基因SHOX2的表达,轻微降低san有害转录因子NKX2-5的表达。结论TBX3在hiPSC向起搏器样细胞分化过程中发挥重要作用,在泛心肌细胞分化过程中调控TBX3的表达可能导致治疗性起搏器细胞的发育。
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TBX3 induces biased differentiation of human induced pluripotent stem cells into cardiac pacemaker-like cells

Background

TBX3 plays a critical role in the formation of the sinoatrial node (SAN) during embryonic heart development. However, the contribution of TBX3 in driving the differentiation of human induced pluripotent stem cells (hiPSC)into pacemaker cells remains to be explored.

Results

Using the pan-cardiomyocyte differentiation protocol of human induced pluripotent stem cells (hiPSC),TBX3 gene was introduced into the differentiating hiPSC on day 5 post-differentiation, and the differentiation of pacemaker-like cardiomyocytes was evaluated on day 21. The results showed that TBX3 significantly induced biased differentiation of hiPSC into pacemaker-like cells as judged by significantly increased expression of SAN-specific marker gene, SHOX2, and slightly decreased expression of SAN-detrimental transcription factor, NKX2-5.

Conclusion

Our results suggest that TBX3 plays an important role in driving the differentiation of hiPSC into pacemaker-like cells, and manipulation of TBX3 expression during pan-cardiomyocyte differentiation may lead to the development of therapeutic pacemaker cells.

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来源期刊
Gene Expression Patterns
Gene Expression Patterns 生物-发育生物学
CiteScore
2.30
自引率
0.00%
发文量
42
审稿时长
35 days
期刊介绍: Gene Expression Patterns is devoted to the rapid publication of high quality studies of gene expression in development. Studies using cell culture are also suitable if clearly relevant to development, e.g., analysis of key regulatory genes or of gene sets in the maintenance or differentiation of stem cells. Key areas of interest include: -In-situ studies such as expression patterns of important or interesting genes at all levels, including transcription and protein expression -Temporal studies of large gene sets during development -Transgenic studies to study cell lineage in tissue formation
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