Key Laboratory of Agricultural Animal Genetics, Breeding, and Reproduction of the Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China.
College of Animal Science and Technology, Shandong Agricultural University, Taian, China.
Stem Cell Rev Rep. 2022 Oct;18(7):2535-2546. doi: 10.1007/s12015-022-10371-7. Epub 2022 Apr 9.
Primordial germ cells (PGCs) are the undifferentiated progenitors of the gametes. Unlike the poor maintenance of cultured mammalian PGCs, the avian PGCs can be expanded in vitro indefinitely while preserving pluripotency and germline competence. In mammals, the Oct4 is the master transcription factor that ensures the stemness of pluripotent cells such as PGCs, but the specific function of Oct4 in chicken PGCs remains unclear. As expected, the loss of Oct4 in chicken PGCs reduced the expression of key pluripotency factors and promoted the genes involved in endoderm and ectoderm differentiation. Furthermore, the global active chromatin was reduced as shown by the depletion of the H3K27ac upon Oct4 suppression. Interestingly, the de-activated chromatin caused the down-regulation of adjacent genes which are mostly known regulators of cell junction, chemotaxis and cell migration. Consequently, the Oct4-deficient PGCs show impaired cell migration and could not colonize the gonads when re-introduced into the bloodstream of the embryo. We propose that, in addition to maintaining pluripotency, the Oct4 mediated chromatin activation is dictating chicken PGC migration.
原始生殖细胞（PGCs）是配子的未分化祖细胞。与培养的哺乳动物 PGC 维持不良不同，禽类 PGC 可以在体外无限期扩增，同时保持多能性和种系能力。在哺乳动物中，Oct4 是确保多能性细胞（如 PGC）干性的主转录因子，但 Oct4 在鸡 PGC 中的具体功能仍不清楚。不出所料，鸡 PGC 中 Oct4 的缺失降低了关键多能性因子的表达，并促进了涉及内胚层和外胚层分化的基因。此外，由于 Oct4 抑制导致 H3K27ac 耗尽，因此全局活性染色质减少。有趣的是，失活的染色质导致相邻基因的下调，这些基因大多是细胞连接、趋化性和细胞迁移的已知调节剂。因此，当缺乏 Oct4 的 PGC 被重新引入胚胎血液时，其迁移能力受损，无法定植于性腺。我们提出，除了维持多能性外，Oct4 介导的染色质激活还决定了鸡 PGC 的迁移。
