The unique developmental characteristics of chicken primordial germ cells (PGCs) enable them to be used in recovery of endangered bird species, gene editing and the generation of transgenic birds, but the limited number of PGCs greatly limits their application. Studies have shown that the formation of mammalian PGCs is induced by BMP4 signal, but the mechanism underlying chicken PGC formation has not been determined. Here, we confirmed that Wnt signaling activated via BMP4 activates transcription of Lin28A by inducing β-catenin to compete with LSD1 for binding to TCF7L2, causing LSD1 to dissociate from the Lin28A promoter and enhancing H3K4me2 methylation in this region. Lin28A promotes PGC formation by inhibiting gga-let7a-3p maturation to initiate Blimp1 expression. Interestingly, expression of Blimp1 helped sustain Wnt5A expression by preventing LSD1 binding to the Wnt5A promoter. We thus elucidated a positive feedback pathway involving Wnt–Lin28A–Blimp1–Wnt that ensures PGC formation. In summary, our data provide new insight into the development of PGCs in chickens.

鸡原始生殖细胞（PGC）独特的发育特性使其可用于濒危鸟类的恢复、基因编辑和转基因鸟类的产生，但PGC的数量有限极大地限制了其应用。研究表明哺乳动物PGC的形成是由BMP4信号诱导的，但鸡PGC形成的机制尚未确定。在这里，我们证实，通过 BMP4 激活的 Wnt 信号传导通过诱导 β-catenin 与LSD1竞争结合 TCF7L2 来激活 Lin28A的转录，导致 LSD1 从Lin28A启动子解离并增强该区域的 H3K4me2 甲基化。Lin28A通过抑制gga-let7a-3p成熟启动Blimp1表达来促进 PGC 形成。有趣的是， Blimp1的表达通过阻止 LSD1 与Wnt5A启动子结合来帮助维持Wnt5A表达。因此，我们阐明了一条涉及 Wnt- Lin28A - Blimp1 -Wnt的正反馈途径，可确保 PGC 的形成。总之，我们的数据为鸡的 PGC 发育提供了新的见解。