Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Stem Cell Reports. 2015 Oct 13;5(4):490-8. doi: 10.1016/j.stemcr.2015.08.014. Epub 2015 Sep 24.
We demonstrate that the pluripotency gene OCT4 has a role in regulating differentiation via Wnt signaling. OCT4 expression levels in human embryonic stem cells increases transiently during the first 24 hr of in vitro differentiation, with OCT4 occupancy increasing at endoderm regulators such as SOX17 and FOXA2. This increased occupancy correlates with loss of the PRC2 complex and the inhibitory histone mark H3K27me3. Knockdown of OCT4 during differentiation inhibits mesendoderm formation and removal of the H3K27me3 mark from the SOX17 promoter, suggesting that OCT4 acts to induce removal of the PRC2 complex. Furthermore, OCT4 and β-catenin can be co-immunoprecipitated upon differentiation, and Wnt stimulation is required for the enhanced OCT4 occupancy and loss of the PRC2 complex from the SOX17 promoter. In conclusion, our study reveals that OCT4, a master regulator of pluripotency, may also collaborate with Wnt signaling to drive endoderm induction by pre-patterning epigenetic markers on endodermal promoters.
我们证明多能性基因 OCT4 通过 Wnt 信号在调节分化中起作用。在体外分化的前 24 小时内，人胚胎干细胞中的 OCT4 表达水平短暂增加，OCT4 占据增加在内胚层调节剂如 SOX17 和 FOXA2 处。这种增加的占据与 PRC2 复合物和抑制性组蛋白标记 H3K27me3 的丢失相关。分化过程中 OCT4 的敲低抑制中胚层形成，并且从 SOX17 启动子上除去 H3K27me3 标记，表明 OCT4 诱导 PRC2 复合物的去除。此外，在分化时 OCT4 和 β-连环蛋白可以共免疫沉淀，并且 Wnt 刺激对于增强 OCT4 占据和从 SOX17 启动子上除去 PRC2 复合物是必需的。总之，我们的研究表明，多能性的主调控因子 OCT4 也可能与 Wnt 信号合作，通过在肠内胚层启动子上预先形成表观遗传标记来驱动内胚层诱导。
Zotero 插件
