MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Cell Stem Cell. 2010 Jun 4;6(6):547-56. doi: 10.1016/j.stem.2010.04.013.
Embryonic stem cells (ESCs) are pluripotent, self-renewing, and have the ability to reprogram differentiated cell types to pluripotency upon cellular fusion. Polycomb-group (PcG) proteins are important for restraining the inappropriate expression of lineage-specifying factors in ESCs. To investigate whether PcG proteins are required for establishing, rather than maintaining, the pluripotent state, we compared the ability of wild-type, PRC1-, and PRC2-depleted ESCs to reprogram human lymphocytes. We show that ESCs lacking either PRC1 or PRC2 are unable to successfully reprogram B cells toward pluripotency. This defect is a direct consequence of the lack of PcG activity because it could be efficiently rescued by reconstituting PRC2 activity in PRC2-deficient ESCs. Surprisingly, the failure of PRC2-deficient ESCs to reprogram somatic cells is functionally dominant, demonstrating a critical requirement for PcG proteins in the chromatin-remodeling events required for the direct conversion of differentiated cells toward pluripotency.
胚胎干细胞（ESCs）具有多能性、自我更新能力，并能在细胞融合时将分化细胞类型重编程为多能性。多梳组（PcG）蛋白对于抑制 ESCs 中谱系特异性因子的不当表达非常重要。为了研究 PcG 蛋白是否需要建立而不是维持多能状态，我们比较了野生型、PRC1-和 PRC2 耗竭的 ESCs 重编程人淋巴细胞的能力。我们发现，缺乏 PRC1 或 PRC2 的 ESCs 无法成功地将 B 细胞重编程为多能性。这种缺陷是 PcG 活性缺失的直接后果，因为它可以通过在 PRC2 缺陷的 ESCs 中重建 PRC2 活性来有效地挽救。令人惊讶的是，PRC2 缺陷的 ESCs 无法重编程体细胞是功能上的优势，这表明 PcG 蛋白在染色质重塑事件中对于直接将分化细胞重编程为多能性是必需的。
