An engineered cardiac reporter cell line identifies human embryonic stem cell-derived myocardial precursors.
An engineered cardiac reporter cell line identifies human embryonic stem cell-derived myocardial precursors.
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DOI：
10.1371/journal.pone.0016004
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发表时间：
2011-01-04
期刊：
影响因子：
3.7
通讯作者：
Bernstein HS
中科院分区：
文献类型：
--
作者：
Ritner C;Wong SS;King FW;Mihardja SS;Liszewski W;Erle DJ;Lee RJ;Bernstein HS
与某些器官不同，心脏在受伤后不能自我修复。人类胚胎干细胞(HESCs)无限期地生长和分裂，同时保持发育成身体许多组织的潜力。因此，它们为治疗以组织丢失为特征的人类疾病提供了前所未有的机会。我们已经使用α-肌球蛋白重链(α)-GFP报告线鉴定了来源于hESCs(HMPS)的早期心肌前体。我们已经通过免疫细胞化学和实时定量聚合酶链式反应(QPCR)证明，报告激活仅限于体外分化的hESC来源的心肌细胞(CMS)，而HMPS在体内畸胎瘤形成实验中仅产生肌肉。我们还证明了该记者不干扰hESC基因组的稳定性。重要的是，我们通过定量聚合酶链式反应和微电极阵列分析表明，HMPS可导致房性、室性和特殊传导CM亚型。HMPs在分化过程中的表达谱提示Wnt和转化生长因子-β信号通路在CM的发生发展中起作用。利用这一αMHC-GFP报告系鉴定HMPs将为研究人类心肌发育的调控途径提供重要的线索，并可能为心脏疾病的治疗提供一种新的治疗试剂。
Unlike some organs, the heart is unable to repair itself after injury. Human embryonic stem cells (hESCs) grow and divide indefinitely while maintaining the potential to develop into many tissues of the body. As such, they provide an unprecedented opportunity to treat human diseases characterized by tissue loss. We have identified early myocardial precursors derived from hESCs (hMPs) using an α-myosin heavy chain (αMHC)-GFP reporter line. We have demonstrated by immunocytochemistry and quantitative real-time PCR (qPCR) that reporter activation is restricted to hESC-derived cardiomyocytes (CMs) differentiated in vitro, and that hMPs give rise exclusively to muscle in an in vivo teratoma formation assay. We also demonstrate that the reporter does not interfere with hESC genomic stability. Importantly, we show that hMPs give rise to atrial, ventricular and specialized conduction CM subtypes by qPCR and microelectrode array analysis. Expression profiling of hMPs over the course of differentiation implicate Wnt and transforming growth factor-β signaling pathways in CM development. The identification of hMPs using this αMHC-GFP reporter line will provide important insight into the pathways regulating human myocardial development, and may provide a novel therapeutic reagent for the treatment of cardiac disease.
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影响因子：
4
作者：
Epting, CL;López, JE;Bernstein, HS
通讯作者：
Bernstein, HS
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
4.8
作者：
Nussbaum, Jeannette;Minami, Elina;Murry, Charles E.
通讯作者：
Murry, Charles E.
影响因子：
37.8
作者：
Mummery, C;Ward-van Oostwaard, D;Tertoolen, L
通讯作者：
Tertoolen, L
影响因子：
20.1
作者：
NG, WA;GRUPP, IL;ROBBINS, J
通讯作者：
ROBBINS, J