Enhanced Function of Induced Pluripotent Stem Cell-Derived Endothelial Cells Through ESM1 Signaling.
Enhanced Function of Induced Pluripotent Stem Cell-Derived Endothelial Cells Through ESM1 Signaling.
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通过ESM1信号传导，诱导多能干细胞衍生的内皮细胞的功能增强。
DOI：
10.1002/stem.2936
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发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Margariti A
中科院分区：
文献类型：
--
作者：
Vilà-González M;Kelaini S;Magee C;Caines R;Campbell D;Eleftheriadou M;Cochrane A;Drehmer D;Tsifaki M;O'Neill K;Pedrini E;Yang C;Medina R;McDonald D;Simpson D;Zampetaki A;Zeng L;Grieve D;Lois N;Stitt AW;Margariti A
（心）血管疾病的死亡率是世界上最高的之一，因此健康的功能性内皮对血管疾病至关重要。在这项研究中，人类诱导多能干细胞（iPS）细胞从1 ml健康供体的血液中重编程，随后分化为具有典型EC特征的内皮细胞（iPS-EC）。这项研究结合了iPS细胞技术和下一代测序，以深入了解iPS-ECs的转录调控。我们确定了内皮细胞特异性分子1（ESM 1）是EC分化过程中表达最高的基因之一，通过调节连接蛋白40（CX 40）和eNOS在EC富集和功能中发挥关键作用。重要的是，ESM 1增强了iPS-EC在体内血管生成和后肢缺血模型中改善血管生成和新血管形成的潜力。这些研究结果首次证明，富集的功能性EC是通过细胞重编程和ESM 1信号传导获得的，为血管疾病的药物筛选和基于细胞的治疗开辟了新的视野。因此，这项研究展示了一种新的方法，通过ESM 1信号转导从极少量血液中富集和增强诱导多能干细胞（iPS）来源的EC的功能，这大大增强了它们的功能并提高了它们的治疗潜力。干细胞2019;37：226-239
The mortality rate for (cardio)‐vascular disease is one of the highest in the world, so a healthy functional endothelium is of outmost importance against vascular disease. In this study, human induced pluripotent stem (iPS) cells were reprogrammed from 1 ml blood of healthy donors and subsequently differentiated into endothelial cells (iPS‐ECs) with typical EC characteristics. This research combined iPS cell technologies and next‐generation sequencing to acquire an insight into the transcriptional regulation of iPS‐ECs. We identified endothelial cell‐specific molecule 1 (ESM1) as one of the highest expressed genes during EC differentiation, playing a key role in EC enrichment and function by regulating connexin 40 (CX40) and eNOS. Importantly, ESM1 enhanced the iPS‐ECs potential to improve angiogenesis and neovascularisation in in vivo models of angiogenesis and hind limb ischemia. These findings demonstrated for the first time that enriched functional ECs are derived through cell reprogramming and ESM1 signaling, opening the horizon for drug screening and cell‐based therapies for vascular diseases. Therefore, this study showcases a new approach for enriching and enhancing the function of induced pluripotent stem (iPS) cell‐derived ECs from a very small amount of blood through ESM1 signaling, which greatly enhances their functionality and increases their therapeutic potential. Stem Cells 2019;37:226–239
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影响因子：
6
作者：
Collado MS;Cole BK;Figler RA;Lawson M;Manka D;Simmers MB;Hoang S;Serrano F;Blackman BR;Sinha S;Wamhoff BR
通讯作者：
Wamhoff BR
DOI：
10.1002/stem.2594
发表时间：
2017-04
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Cochrane A;Kelaini S;Tsifaki M;Bojdo J;Vilà-González M;Drehmer D;Caines R;Magee C;Eleftheriadou M;Hu Y;Grieve D;Stitt AW;Zeng L;Xu Q;Margariti A
通讯作者：
Margariti A
影响因子：
14.8
作者：
通讯作者：
--
DOI：
10.1002/stem.2820
发表时间：
2018-07
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Kelaini S;Vilà-González M;Caines R;Campbell D;Eleftheriadou M;Tsifaki M;Magee C;Cochrane A;O'neill K;Yang C;Stitt AW;Zeng L;Grieve DJ;Margariti A
通讯作者：
Margariti A
影响因子：
4
作者：
Kokudo, Takashi;Suzuki, Yuka;Miyazono, Kohei
通讯作者：
Miyazono, Kohei