AW551984: a novel regulator of cardiomyogenesis in pluripotent embryonic cells.
AW551984: a novel regulator of cardiomyogenesis in pluripotent embryonic cells.
复制标题
AW551984：多能胚胎细胞心肌发生的新型调节剂。
作者：
S. Yasuda;Tetsuya Hasegawa;T. Hosono;Mitsutoshi Satoh;Keiichi Watanabe;Kageyoshi Ono;S. Shimizu;T. Hayakawa;Teruhide Yamaguchi;Kazuhiro Suzuki;Yoji Sato
了解调节多能干细胞心脏分化的机制对于作为细胞治疗产品的心肌细胞的有效产生和扩增是必要的。在目前的研究中，我们已经确定了调节多能胚胎细胞心脏分化的基因。我们分离了在心肌发生中具有不同特性的P19CL6细胞亚系，并通过转录组分析提取了24个与心肌发生相关的CMR（心肌发生相关候选基因）。通过RNAi （RNA干扰）敲除CMR基因，发现18个基因影响EC（胚胎癌）细胞中心脏标记基因的自发收缩或转录水平。我们还在小鼠胚胎干细胞中敲低CMR基因，并诱导体外心脏分化。3个CMR基因AW551984、2810405K02Rik （RIKEN cDNA 2810405K02基因）和Cd302 （Cd302抗原）调节EC细胞和ES细胞的心脏分化。AW551984的缺失降低了早期心脏转录因子Nkx2.5 （NK2转录因子相关位点5）的表达，但不影响胚胎干细胞分化过程中多能性和早期中胚层标记基因的转录水平。激活Wnt/β-catenin信号可以增强胚状体形成过程中ES细胞中AW551984和Nkx2.5的表达。我们的研究结果表明，AW551984是多能胚胎细胞心肌形成的一种新的调节因子，它将Wnt/β-catenin信号传导与Nkx2.5的表达联系起来。
An understanding of the mechanism that regulates the cardiac differentiation of pluripotent stem cells is necessary for the effective generation and expansion of cardiomyocytes as cell therapy products. In the present study, we have identified genes that modulate the cardiac differentiation of pluripotent embryonic cells. We isolated P19CL6 cell sublines that possess distinct properties in cardiomyogenesis and extracted 24 CMR (cardiomyogenesis-related candidate) genes correlated with cardiomyogenesis using a transcriptome analysis. Knockdown of the CMR genes by RNAi (RNA interference) revealed that 18 genes influence spontaneous contraction or transcript levels of cardiac marker genes in EC (embryonal carcinoma) cells. We also performed knockdown of the CMR genes in mouse ES (embryonic stem) cells and induced in vitro cardiac differentiation. Three CMR genes, AW551984, 2810405K02Rik (RIKEN cDNA 2810405K02 gene) and Cd302 (CD302 antigen), modulated the cardiac differentiation of both EC cells and ES cells. Depletion of AW551984 attenuated the expression of the early cardiac transcription factor Nkx2.5 (NK2 transcription factor related locus 5) without affecting transcript levels of pluripotency and early mesoderm marker genes during ES cell differentiation. Activation of Wnt/β-catenin signalling enhanced the expression of both AW551984 and Nkx2.5 in ES cells during embryoid body formation. Our findings indicate that AW551984 is a novel regulator of cardiomyogenesis from pluripotent embryonic cells, which links Wnt/β-catenin signalling to Nkx2.5 expression.
DOI：
10.1073/pnas.98.2.615
发表时间：
2001-01
影响因子：
11.1
作者：
K. Caron;O. Smithies
通讯作者：
K. Caron;O. Smithies