Differentiation of mesenchymal stem cells and embryonic stem cells into steroidogenic cells using steroidogenic factor-1 and liver receptor homolog-1
Differentiation of mesenchymal stem cells and embryonic stem cells into steroidogenic cells using steroidogenic factor-1 and liver receptor homolog-1
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DOI：
10.1016/j.mce.2010.11.025
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发表时间：
2011-04
影响因子：
4.1
通讯作者：
T. Yazawa;Shinya Kawabe;Y. Inaoka;R. Okada;T. Mizutani;Yoshitaka Imamichi;Yunfeng Ju;Yukiko Yamazaki;Y. Usami;Mayu Kuribayashi;A. Umezawa;K. Miyamoto
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文献类型：
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作者：
T. Yazawa;Shinya Kawabe;Y. Inaoka;R. Okada;T. Mizutani;Yoshitaka Imamichi;Yunfeng Ju;Yukiko Yamazaki;Y. Usami;Mayu Kuribayashi;A. Umezawa;K. Miyamoto
此前，我们已经证明间充质干细胞可以通过类固醇生成因子-1和8溴-cAMP处理分化为类固醇生成细胞。使用肝受体同源物-1（核受体5A家族核受体的另一种）与8溴-cAMP一起使用也导致人间充质干细胞分化为类固醇激素产生细胞。相同的方法不能应用于其他未分化细胞，例如胚胎干细胞或胚胎癌细胞，因为核受体5A家族的过度表达对这些细胞具有细胞毒性。我们建立了在 ROSA26 位点携带四环素调节类固醇生成因子 1 基因的胚胎干细胞。通过在 IV 型胶原包被的培养皿上培养并在表达类固醇生成因子 1 之前用视黄酸脉冲暴露进行处理，胚胎干细胞首先分化为间充质细胞谱系。尽管在缺乏白血病抑制因子的情况下，未处理的胚胎干细胞由于细胞无法存活而不能通过表达类固醇生成因子1而转化为类固醇生成细胞，但当诱导类固醇生成因子1的表达时，分化的细胞可以成功地转化为类固醇生成细胞。它们表现出类肾上腺皮质细胞的特征，并产生大量的皮质酮。这些结果表明，多能干细胞可以通过间充质细胞谱系通过核受体5A蛋白家族分化为类固醇生成细胞。这种方法可能为未来针对类固醇生成缺陷引起的疾病的基因治疗提供细胞来源。
Previously, we have demonstrated that mesenchymal stem cells could be differentiated into steroidogenic cells through steroidogenic factor-1 and 8bromo-cAMP treatment. Use of liver receptor homolog-1, another of the nuclear receptor 5A family nuclear receptors, with 8bromo-cAMP also resulted in the differentiation of human mesenchymal stem cells into steroid hormone-producing cells. The same approaches could not be applied to other undifferentiated cells such as embryonic stem cells or embryonal carcinoma cells, because the over-expression of the nuclear receptor 5A family is cytotoxic to these cells. We established embryonic stem cells carrying tetracycline-regulated steroidogenic factor-1 gene at the ROSA26 locus. The embryonic stem cells were first differentiated into a mesenchymal cell lineage by culturing on collagen IV-coated dishes and treating with pulse exposures of retinoic acid before expression of steroidogenic factor-1. Although the untreated embryonic stem cells could not be converted into steroidogenic cells by expression of steroidogenic factor-1 in the absence of leukemia inhibitory factor due to inability of the cells to survive, the differentiated cells could be successfully converted into steroidogenic cells when expression of steroidogenic factor-1 was induced. They exhibited characteristics of adrenocortical-like cells and produced a large amount of corticosterone. These results indicated that pluripotent stem cells could be differentiated into steroidogenic cells by the nuclear receptor 5A family of protein via the mesenchymal cell lineage. This approach may provide a source of cells for future gene therapy for diseases caused by steroidogenesis deficiencies.