Generation of human vascular smooth muscle subtypes provides insight into embryological origin-dependent disease susceptibility.
Generation of human vascular smooth muscle subtypes provides insight into embryological origin-dependent disease susceptibility.
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DOI：
10.1038/nbt.2107
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发表时间：
2012-01-15
影响因子：
46.9
通讯作者：
中科院分区：
文献类型：
--
作者：
胚胎起源的异质性是血管平滑肌细胞（SMC）的一个标志，这可能影响血管疾病的发展。人多能干细胞（hPSC）分化成发育起源特异性SMC亚型仍然是难以捉摸的。在这项研究中，我们已经建立了一个化学定义的方案，其中hPSC最初被诱导形成神经外胚层，侧板中胚层或近轴中胚层。这些中间群体进一步分化为SMC（> 80%MYH 11+和ACTA 2+），其显示出响应于血管收缩剂的收缩能力并在体内覆盖血管周围区域。衍生的SMC亚型概括了先前使用不同来源的主动脉SMC研究中记录的对细胞因子的独特增殖和分泌反应。重要的是，该系统预测了来自侧板中胚层的SMC的细胞外基质降解增加，这使用来自相应来源的大鼠主动脉SMC证实。总的来说，这项工作将在建模起源依赖性疾病易感性和再生医学的生物工程血管移植物中具有广泛的应用。
Heterogeneity of embryological origins is a hallmark of vascular smooth muscle cells (SMCs), which may influence vascular disease development. Differentiation of human pluripotent stem cells (hPSCs) into developmental origin-specific SMC subtypes remains elusive. In this study, we have established a chemically defined protocol where hPSCs were initially induced to form neuroectoderm, lateral plate mesoderm or paraxial mesoderm. These intermediate populations were further differentiated towards SMCs (>80% MYH11+ and ACTA2+) which displayed contractile ability in response to vasoconstrictors and invested perivascular regions in vivo. Derived SMC subtypes recapitulated the unique proliferative and secretory responses to cytokines previously documented in studies using aortic SMCs of distinct origins. Importantly, this system predicted increased extracellular matrix degradation by SMCs derived from lateral plate mesoderm, which was confirmed using rat aortic SMCs from corresponding origins. Collectively, this work will have broad applications in modeling origin-dependent disease susceptibility and in bio-engineered vascular grafts for regenerative medicine.
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影响因子：
5.2
作者：
McLean, Amanda B.;D'Amour, Kevin A.;Dalton, Stephen
通讯作者：
Dalton, Stephen
DOI：
10.1073/pnas.0503741102
发表时间：
2005-06-21
影响因子：
11.1
作者：
Li, J;Zhu, XH;Parmacek, MS
通讯作者：
Parmacek, MS
DOI：
10.1073/pnas.0507346102
发表时间：
2005-10-18
影响因子：
11.1
作者：
Oh, JY;Richardson, JA;Olson, EN
通讯作者：
Olson, EN
影响因子：
2.7
作者：
Mikawa, T;Gourdie, RG
通讯作者：
Gourdie, RG
影响因子：
6.2
作者：
Leroux-Berger, Margot;Queguiner, Isabelle;Kempf, Herve
通讯作者：
Kempf, Herve