Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, University Hospital, 45122 Essen, North Rhine-Westphalia, Germany.
Sci Rep. 2013 Oct 22;3:2178. doi: 10.1038/srep02178.
Human vascular wall-resident CD44+ multipotent stem cells (VW-MPSCs) within the vascular adventitia are capable to differentiate into pericytes and smooth muscle cells (SMC). This study demonstrates HOX-dependent differentiation of CD44(+) VW-MPSCs into SMC that involves epigenetic modification of transgelin as a down-stream regulated gene. First, HOXB7, HOXC6 and HOXC8 were identified to be differentially expressed in VW-MPSCs as compared to terminal differentiated human aortic SMC, endothelial cells and undifferentiated pluripotent embryonic stem cells. Silencing these HOX genes in VW-MPSCs significantly reduced their sprouting capacity and increased expression of the SMC markers transgelin and calponin and the histone gene histone H1. Furthermore, the methylation pattern of the TAGLN promoter was altered. In summary, our findings suggest a role for certain HOX genes in regulating differentiation of human VW-MPSC into SMCs that involves epigenetic mechanisms. This is critical for understanding VW-MPSC-dependent vascular disease processes such as neointima formation and tumor vascularization.
人血管壁驻留的 CD44+多能干细胞（VW-MPSCs）位于血管外膜中，能够分化为周细胞和平滑肌细胞（SMC）。本研究表明，HOX 依赖性 CD44(+)VW-MPSC 向 SMC 的分化涉及作为下游调节基因的转谷氨酰胺酶的表观遗传修饰。首先，与终末分化的人主动脉 SMC、内皮细胞和未分化的多能胚胎干细胞相比，HOXB7、HOXC6 和 HOXC8 在 VW-MPSCs 中被鉴定为差异表达。在 VW-MPSCs 中沉默这些 HOX 基因，显著降低了其发芽能力，并增加了 SMC 标志物转谷氨酰胺酶和钙调蛋白以及组蛋白基因组蛋白 H1 的表达。此外，TAGLN 启动子的甲基化模式发生了改变。总之，我们的研究结果表明，某些 HOX 基因在调节人 VW-MPSC 向 SMC 的分化中起作用，涉及表观遗传机制。这对于理解 VW-MPSC 依赖性血管疾病过程，如新生内膜形成和肿瘤血管生成，至关重要。
