Cell population balance of cardiovascular spheroids derived from human induced pluripotent stem cells
Cell population balance of cardiovascular spheroids derived from human induced pluripotent stem cells
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人诱导多能干细胞来源的心血管球体的细胞群平衡
DOI：
10.1038/s41598-018-37686-1
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发表时间：
2019
影响因子：
4.6
通讯作者：
Li, Yan
中科院分区：
文献类型：
--
作者：
Yan, Yuanwei;Bejoy, Julie;Xia, Junfei;Griffin, Kyle;Guan, Jingjiao;Li, Yan
干细胞衍生的心肌细胞和血管细胞可用于各种应用，例如研究人类心脏发育和在培养中模拟人类疾病。特别地，基于Wnt信号传导的调节的方案能够从人多能干细胞（hPSC）产生高质量的心肌细胞或血管细胞。然而，3D心血管球体发育成血管或心脏细胞背后的机制尚未得到很好的探索。Hippo/Yes相关蛋白（雅普）信号通路在器官发生的调控中起重要作用，但其对心血管分化的影响研究较少。在这项研究中，评价了接种密度和雅普信号传导的变化对来自hPSC的3D心血管球体图案化的影响。与2D培养相比，3D心血管球体显示出更高水平的肌节条纹和更高的α-辅肌动蛋白+细胞的长宽比。高接种密度的球状体中α-辅肌动蛋白阳性细胞较多，核雅普表达较少。还用不同的小分子处理3D心血管球体，包括Rho激酶抑制剂（Y27632）、细胞松弛素D、达沙替尼和溶血磷脂酸以调节雅普定位。核雅普抑制导致活性β-catenin（血管标记物）和MRTF（由RhoGTPases介导的转录因子）的表达降低。Y27632还促进MMP-2/-3（基质重塑）和Notch-1（Notch信号传导）的基因表达。这些结果应该有助于我们理解从hPSC形成中胚层后心血管球状体的有效图案化的潜在影响。
Stem cell-derived cardiomyocytes and vascular cells can be used for a variety of applications such as studying human heart development and modelling human disease in culture. In particular, protocols based on modulation of Wnt signaling were able to produce high quality of cardiomyocytes or vascular cells from human pluripotent stem cells (hPSCs). However, the mechanism behind the development of 3D cardiovascular spheroids into either vascular or cardiac cells has not been well explored. Hippo/Yes-associated protein (YAP) signaling plays important roles in the regulation of organogenesis, but its impact on cardiovascular differentiation has been less evaluated. In this study, the effects of seeding density and a change in YAP signaling on 3D cardiovascular spheroids patterning from hPSCs were evaluated. Compared to 2D culture, 3D cardiovascular spheroids exhibited higher levels of sarcomeric striations and higher length-to-width ratios of α-actinin+cells. The spheroids with high seeding density exhibited more α-actinin+cells and less nuclear YAP expression. The 3D cardiovascular spheroids were also treated with different small molecules, including Rho kinase inhibitor (Y27632), Cytochalasin D, Dasatinib, and Lysophosphatidic acid to modulate YAP localization. Nuclear YAP inhibition resulted in lower expression of active β-catenin, vascular marker, and MRTF, the transcription factor mediated by RhoGTPases. Y27632 also promoted the gene expression of MMP-2/-3 (matrix remodeling) and Notch-1 (Notch signaling). These results should help our understanding of the underlying effects for the efficient patterning of cardiovascular spheroids after mesoderm formation from hPSCs.
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影响因子：
23.9
作者：
Burridge, Paul W.;Keller, Gordon;Gold, Joseph D.;Wu, Joseph C.
通讯作者：
Wu, Joseph C.
DOI：
--
发表时间：
2005
期刊：
--
影响因子：
--
作者：
G. Davis;D. Senger
通讯作者：
G. Davis;D. Senger
影响因子：
9.7
作者：
Yuanwei Yan;Julie Bejoy;Junfei Xia;J. Guan;Yi Zhou;Yan Li
通讯作者：
Yuanwei Yan;Julie Bejoy;Junfei Xia;J. Guan;Yi Zhou;Yan Li
人多能干细胞培养密度调节YAP信号传导。
影响因子：
4.7
作者：
Hsiao C;Lampe M;Nillasithanukroh S;Han W;Lian X;Palecek SP
通讯作者：
Palecek SP
影响因子：
2.7
作者：
Xu C;Police S;Hassanipour M;Li Y;Chen Y;Priest C;O'Sullivan C;Laflamme MA;Zhu WZ;Van Biber B;Hegerova L;Yang J;Delavan-Boorsma K;Davies A;Lebkowski J;Gold JD
通讯作者：
Gold JD