Comprehensive gene-expression survey identifies wif1 as a modulator of cardiomyocyte differentiation.

Comprehensive gene-expression survey identifies wif1 as a modulator of cardiomyocyte differentiation.
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DOI:
10.1371/journal.pone.0015504
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发表时间:
2010-12-13
期刊:
影响因子:
3.7
通讯作者:
't Hoen PA
't Hoen PA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Buermans HP;van Wijk B;Hulsker MA;Smit NC;den Dunnen JT;van Ommen GB;Moorman AF;van den Hoff MJ;'t Hoen PA

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在鸡心脏发育过程中,心外膜(PE)形成心外膜(Epi),它有助于心脏内的几种非心肌谱系。与 Epi 外植体培养相反,PE 外植体可以分化为心肌细胞表型。通过PE外植体培养物和成熟Epi细胞的时间微阵列表达谱,我们鉴定了与向这些谱系的分化特异性相关的基因以及与Epi谱系限制相关的基因。我们发现 Wnt 信号传导在确定不同细胞谱系中发挥着核心作用。 PE 外植体培养物中重组蛋白孵育后的免疫荧光染色表明,早期上调的 Wnt 抑制因子 1 (Wif1) 以与 Wnt 刺激类似的方式刺激心肌细胞分化。相应地,在小鼠多能胚胎性癌细胞系 p19cl6 中,早期和晚期 Wif1 暴露分别增强和减弱分化。 HH12 鸡胚心脏在卵内暴露于 Wif1 会增加 Tbx18 阳性心脏祖细胞库。这些数据表明 Wif1 增强心肌生成。
During chicken cardiac development the proepicardium (PE) forms the epicardium (Epi), which contributes to several non-myocardial lineages within the heart. In contrast to Epi-explant cultures, PE explants can differentiate into a cardiomyocyte phenotype. By temporal microarray expression profiles of PE-explant cultures and maturing Epi cells, we identified genes specifically associated with differentiation towards either of these lineages and genes that are associated with the Epi-lineage restriction. We found a central role for Wnt signaling in the determination of the different cell lineages. Immunofluorescent staining after recombinant-protein incubation in PE-explant cultures indicated that the early upregulated Wnt inhibitory factor-1 (Wif1), stimulates cardiomyocyte differentiation in a similar manner as Wnt stimulation. Concordingly, in the mouse pluripotent embryogenic carcinoma cell line p19cl6, early and late Wif1 exposure enhances and attenuates differentiation, respectively. In ovo exposure of the HH12 chicken embryonic heart to Wif1 increases the Tbx18-positive cardiac progenitor pool. These data indicate that Wif1 enhances cardiomyogenesis.
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