Apelin enhances directed cardiac differentiation of mouse and human embryonic stem cells.
Apelin enhances directed cardiac differentiation of mouse and human embryonic stem cells.
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DOI：
10.1371/journal.pone.0038328
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Yang PC
中科院分区：
文献类型：
--
作者：
Wang IN;Wang X;Ge X;Anderson J;Ho M;Ashley E;Liu J;Butte MJ;Yazawa M;Dolmetsch RE;Quertermous T;Yang PC
Apelin 是孤儿 G 蛋白偶联受体（APJ 受体）的肽配体，作为中胚层细胞迁移的关键梯度，注定有助于心肌谱系。本研究旨在建立强大的心脏分化方案，特别是评估 apelin 对小鼠和人类胚胎干细胞（mESC 和 hESC）定向分化为心脏谱系的影响。评估不同浓度的apelin（50、100、500 nM）以确定其分化潜力。然后将优化剂量的 apelin 与中胚层分化因子（包括 BMP-4、激活素 A 和 bFGF）以发育特定的时间序列组合，以检查对心脏分化的协同作用。分析了 apelin 诱导的收缩胚状体 (EB) 的细胞、分子和生理特征。结果发现，100 nM apelin 对 mESC 的收缩 EB 百分比最高，而 500 nM 对 hESC 的影响最高。从功能上讲，mESC 衍生的 EB (mEB) 的收缩频率对异丙肾上腺素和地尔硫卓浓度的增加有适当的反应。在apelin治疗组中证实了心脏特异性标记物的阳性表型。该方案由 apelin 和中胚层分化因子组成，可诱导显着更高百分比的 hESC 衍生 EB (hEB) 的收缩性，上调心脏特异性基因和细胞表面标记，并增加收缩力。总之，我们证明 apelin 的治疗增强了小鼠和人类 ESC 的心脏分化，并与中胚层分化因子表现出协同作用。
Apelin is a peptide ligand for an orphan G-protein coupled receptor (APJ receptor) and serves as a critical gradient for migration of mesodermal cells fated to contribute to the myocardial lineage. The present study was designed to establish a robust cardiac differentiation protocol, specifically, to evaluate the effect of apelin on directed differentiation of mouse and human embryonic stem cells (mESCs and hESCs) into cardiac lineage. Different concentrations of apelin (50, 100, 500 nM) were evaluated to determine its differentiation potential. The optimized dose of apelin was then combined with mesodermal differentiation factors, including BMP-4, activin-A, and bFGF, in a developmentally specific temporal sequence to examine the synergistic effects on cardiac differentiation. Cellular, molecular, and physiologic characteristics of the apelin-induced contractile embryoid bodies (EBs) were analyzed. It was found that 100 nM apelin resulted in highest percentage of contractile EB for mESCs while 500 nM had the highest effects on hESCs. Functionally, the contractile frequency of mESCs-derived EBs (mEBs) responded appropriately to increasing concentration of isoprenaline and diltiazem. Positive phenotype of cardiac specific markers was confirmed in the apelin-treated groups. The protocol, consisting of apelin and mesodermal differentiation factors, induced contractility in significantly higher percentage of hESC-derived EBs (hEBs), up-regulated cardiac-specific genes and cell surface markers, and increased the contractile force. In conclusion, we have demonstrated that the treatment of apelin enhanced cardiac differentiation of mouse and human ESCs and exhibited synergistic effects with mesodermal differentiation factors.
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DOI：
10.1084/jem.20061916
发表时间：
2007-02-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Behfar A;Perez-Terzic C;Faustino RS;Arrell DK;Hodgson DM;Yamada S;Puceat M;Niederländer N;Alekseev AE;Zingman LV;Terzic A
通讯作者：
Terzic A
影响因子：
37.8
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Roger VL;Go AS;Lloyd-Jones DM;Benjamin EJ;Berry JD;Borden WB;Bravata DM;Dai S;Ford ES;Fox CS;Fullerton HJ;Gillespie C;Hailpern SM;Heit JA;Howard VJ;Kissela BM;Kittner SJ;Lackland DT;Lichtman JH;Lisabeth LD;Makuc DM;Marcus GM;Marelli A;Matchar DB;Moy CS;Mozaffarian D;Mussolino ME;Nichol G;Paynter NP;Soliman EZ;Sorlie PD;Sotoodehnia N;Turan TN;Virani SS;Wong ND;Woo D;Turner MB;American Heart Association Statistics Committee and Stroke Statistics Subcommittee
通讯作者：
American Heart Association Statistics Committee and Stroke Statistics Subcommittee
影响因子：
2.7
作者：
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通讯作者：
Asashima, Makoto
DOI：
10.1006/bbrc.1998.9489
发表时间：
1998-10-20
影响因子：
3.1
作者：
Tatemoto, K;Hosoya, M;Fujino, M
通讯作者：
Fujino, M
影响因子：
5
作者：
Dai, Tieying;Ramirez-Correa, Genaro;Gao, Wei Dong
通讯作者：
Gao, Wei Dong