Department of Bioengineering, University of California, Berkeley, California 94720, USA.
Nat Commun. 2012 Jun 6;3:875. doi: 10.1038/ncomms1867.
It is generally accepted that the de-differentiation of smooth muscle cells, from the contractile to the proliferative/synthetic phenotype, has an important role during vascular remodelling and diseases. Here we provide evidence that challenges this theory. We identify a new type of stem cell in the blood vessel wall, named multipotent vascular stem cells. Multipotent vascular stem cells express markers, including Sox17, Sox10 and S100β, are cloneable, have telomerase activity, and can differentiate into neural cells and mesenchymal stem cell-like cells that subsequently differentiate into smooth muscle cells. On the other hand, we perform lineage tracing with smooth muscle myosin heavy chain as a marker and find that multipotent vascular stem cells and proliferative or synthetic smooth muscle cells do not arise from the de-differentiation of mature smooth muscle cells. In response to vascular injuries, multipotent vascular stem cells, instead of smooth muscle cells, become proliferative, and differentiate into smooth muscle cells and chondrogenic cells, thus contributing to vascular remodelling and neointimal hyperplasia. These findings support a new hypothesis that the differentiation of multipotent vascular stem cells, rather than the de-differentiation of smooth muscle cells, contributes to vascular remodelling and diseases.
人们普遍认为，平滑肌细胞从收缩型向增殖/合成表型的去分化在血管重塑和疾病中起着重要作用。在这里，我们提供了挑战这一理论的证据。我们在血管壁中鉴定出一种新型的干细胞，命名为多能血管干细胞。多能血管干细胞表达标志物，包括 Sox17、Sox10 和 S100β，具有克隆能力、端粒酶活性，并能分化为神经细胞和间充质干细胞样细胞，随后分化为平滑肌细胞。另一方面，我们进行了谱系追踪，以平滑肌肌球蛋白重链作为标记，发现多能血管干细胞和增殖或合成的平滑肌细胞不是由成熟的平滑肌细胞去分化而来的。在血管损伤后，多能血管干细胞而非平滑肌细胞增殖，并分化为平滑肌细胞和成软骨细胞，从而促进血管重塑和新生内膜增生。这些发现支持了一个新的假说，即多能血管干细胞的分化而不是平滑肌细胞的去分化，有助于血管重塑和疾病的发生。
