Cell sex affects extracellular matrix protein expression and proliferation of smooth muscle progenitor cells derived from human pluripotent stem cells.
Cell sex affects extracellular matrix protein expression and proliferation of smooth muscle progenitor cells derived from human pluripotent stem cells.
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DOI：
10.1186/s13287-017-0606-2
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发表时间：
2017-07-04
影响因子：
7.5
通讯作者：
Chen B
中科院分区：
文献类型：
--
作者：
Li Y;Wen Y;Green M;Cabral EK;Wani P;Zhang F;Wei Y;Baer TM;Chen B
从人类多能干细胞（hPSCs）分化而来的平滑肌祖细胞（pSMCs）在治疗涉及平滑肌病变的疾病或退行性疾病方面具有很大的前景。然而，来自男性和女性的psmc的治疗潜力可能非常不同。细胞性别对干细胞向体细胞的分化过程有着深远的影响。尽管干细胞翻译技术取得了进展，但细胞性别的作用和性激素对间充质系pSMCs分化的影响在很大程度上仍未被探索。采用标准分化方法，将2个人类胚胎干细胞系（1男1女）和3个诱导多能干细胞系（1男2女）分化为pSMCs。我们研究了雄性和雌性hPSCs向pSMCs分化的差异，并研究了17β-雌二醇（E2）对pSMCs细胞外基质（ECM）代谢和细胞增殖率的影响。统计学分析采用Student’s t检验或双因素方差分析，p < 0.05。在标准分化方案下，雄性和雌性hPSCs具有相似的分化效率，并产生形态相似的pSMCs，但衍生的pSMCs在ECM蛋白（如MMP-2和TIMP-1）的表达和细胞增殖率方面存在性别差异。E2处理诱导了雌性pSMCs中肌源性基因标记的表达，并通过降低MMP活性和增加TIMP-1的表达来抑制ECM降解活性，而在雄性pSMCs中则没有。不同性别的hpsc衍生的pSMCs表现出不同的ECM蛋白表达和增殖率。雌激素似乎在雌性pSMCs中促进成熟和ECM蛋白表达，而在雄性pSMCs中则没有。这些数据表明，内在的细胞性别差异可能影响祖细胞生物学。本文的在线版本（doi:10.1186/s13287-017-0606-2）包含补充材料，可供授权用户使用。
Smooth muscle progenitor cells (pSMCs) differentiated from human pluripotent stem cells (hPSCs) hold great promise for treating diseases or degenerative conditions involving smooth muscle pathologies. However, the therapeutic potential of pSMCs derived from men and women may be very different. Cell sex can exert a profound impact on the differentiation process of stem cells into somatic cells. In spite of advances in translation of stem cell technologies, the role of cell sex and the effect of sex hormones on the differentiation towards mesenchymal lineage pSMCs remain largely unexplored. Using a standard differentiation protocol, two human embryonic stem cell lines (one male line and one female line) and three induced pluripotent stem cell lines (one male line and two female lines) were differentiated into pSMCs. We examined differences in the differentiation of male and female hPSCs into pSMCs, and investigated the effect of 17β-estradiol (E2) on the extracellular matrix (ECM) metabolisms and cell proliferation rates of the pSMCs. Statistical analyses were performed by using Student’s t test or two-way ANOVA, p < 0.05. Male and female hPSCs had similar differentiation efficiencies and generated morphologically comparable pSMCs under a standard differentiation protocol, but the derived pSMCs showed sex differences in expression of ECM proteins, such as MMP-2 and TIMP-1, and cell proliferation rates. E2 treatment induced the expression of myogenic gene markers and suppressed ECM degradation activities through reduction of MMP activity and increased expression of TIMP-1 in female pSMCs, but not in male pSMCs. hPSC-derived pSMCs from different sexes show differential expression of ECM proteins and proliferation rates. Estrogen appears to promote maturation and ECM protein expression in female pSMCs, but not in male pSMCs. These data suggest that intrinsic cell-sex differences may influence progenitor cell biology. The online version of this article (doi:10.1186/s13287-017-0606-2) contains supplementary material, which is available to authorized users.