Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, 3430 Litton-Reaves Hall (0306), Blacksburg, VA, 24060, USA.
BMC Dev Biol. 2021 Jan 12;21(1):3. doi: 10.1186/s12861-020-00235-z.
Interleukin-6 (IL6) was recently identified as an embryotrophic factor in bovine embryos, where it acts primarily to mediate inner cell mass (ICM) size. This work explored whether IL6 affects epiblast (EPI) and primitive endoderm (PE) development, the two embryonic lineages generated from the ICM after its formation. Nuclear markers for EPI (NANOG) and PE (GATA6) were used to differentiate the two cell types.
Increases (P < 0.05) in total ICM cell numbers and PE cell numbers were detected in bovine blastocysts at day 8 and 9 post-fertilization after exposure to 100 ng/ml recombinant bovine IL6. Also, IL6 increased (P < 0.05) the number of undifferentiated ICM cells (cells containing both PE and EPI markers). The effects of IL6 on EPI cell numbers were inconsistent. Studies were also completed to explore the importance of Janus kinase 2 (JAK2)-dependent signaling in bovine PE cells. Definitive activation of STAT3, a downstream target for JAK2, was observed in PE cells. Also, pharmacological inhibition of JAK2 decreased (P < 0.05) PE cell numbers.
To conclude, IL6 manipulates ICM development after EPI/PE cell fates are established. The PE cells are the target for IL6, where a JAK-dependent signal is used to regulate PE numbers.
白细胞介素 6(IL6)最近被鉴定为牛胚胎中的一种胚胎营养因子,它主要作用是调节内细胞团(ICM)的大小。这项工作探讨了白细胞介素 6 是否影响上胚层(EPI)和原始内胚层(PE)的发育,这两种胚胎谱系是由 ICM 形成后产生的。EPI 的核标记物(NANOG)和 PE 的核标记物(GATA6)用于区分这两种细胞类型。
在牛胚胎 8 天和 9 天受精后,暴露于 100ng/ml 重组牛白细胞介素 6 后,总 ICM 细胞数和 PE 细胞数增加(P<0.05)。此外,白细胞介素 6 增加了(P<0.05)未分化的 ICM 细胞(同时含有 PE 和 EPI 标记物的细胞)的数量。白细胞介素 6 对 EPI 细胞数量的影响不一致。还完成了研究,以探讨 Janus 激酶 2(JAK2)依赖性信号在牛 PE 细胞中的重要性。PE 细胞中观察到 JAK2 的下游靶标 STAT3 的明确激活。此外,JAK2 的药理学抑制降低了(P<0.05)PE 细胞的数量。
总之,白细胞介素 6 在 EPI/PE 细胞命运确定后操纵 ICM 的发育。PE 细胞是白细胞介素 6 的靶标,JAK 依赖性信号用于调节 PE 数量。