近期，我院动物及医学方向在Molecular Cancer、Nucleic Acids Research、Cell Death & Differentiation、Theranostics等主流期刊上发表论文12篇，在生殖、代谢及发育，疾病发病机制及治疗等领域取得了一系列前沿成果。
生殖领域：张华课题组通过构建对卵巢颗粒可视化在体追踪的小鼠模型，对卵巢颗粒细胞瘤谱系发生及致病机制进行了探索，并发现卵巢颗粒细胞发生大规模的致癌突变后，相关细胞经历了增殖、清理和克隆选择等过程，最终逃逸的单颗突变细胞即可转化为卵巢颗粒细胞癌。同时，相关研究表明Cd24及Cd47可能在人类颗粒细胞瘤中发挥着重要作用（Niu et al., 2023）；同时，张华课题组张焱副教授独立通讯解析了Pcgf2转录调节孕酮受体表达进而调控卵巢排卵和雌性生育的机制；颗粒细胞中缺失Pcgf2导致卵泡排卵异常，并诱发高龄小鼠一系列生殖缺陷，提示了Pcgf2在卵巢衰老中可能具有重要调控作用（Wang et al., 2022）。张华课题组同时受邀在Ebiomedicine发表短评，对LONP1在临床实践中提高卵母细胞质量的可能性进行了展望（Mu and Zhang, 2022）。王超课题组发现SP1直接调控铁氧蛋白Fdx1的转录参与颗粒细胞胆固醇代谢过程，上调mTOR信号通路，促进原始卵泡向初级卵泡的转变。该研究对于加深卵泡发育和消耗相关调控机制的理解以及阐释临床卵巢功能不全分子机制具有重要意义（Zhou et al., 2023）。王超课题组还证明了前颗粒细胞分泌的FGF23通过激活围产期小鼠卵巢中FGFR1下游的p38 MAPK通路防止卵母细胞过早凋亡，对于理解原始卵泡形成的生理调节至关重要（Zhu et al., 2023）。侯云鹏课题组证明了线粒体 Ca2+在维持线粒体功能和调节卵母细胞的表观遗传学修饰方面发挥作用，也证明了线粒体Ca2+调节的MAPK信号传导的影响表观遗传学修饰的新机制（Zhang et al., 2022）。刘佳利课题组先后揭示了多种RNA结合蛋白在两性配子发生和成熟中的重要作用。其中SRSF1通过可变剪切直接结合并调节原发性卵巢功能不全相关基因Six6os1和Msh5的表达促进减数分裂前期I阶段（Sun et al., 2023）；而特异性敲除SRSF2通过下调增殖和凋亡相关的关键基因抑制了胎儿支持细胞增殖，并在生后第14天诱导曲精小管异常凋亡和严重的DNA损伤，导致无法产生正常的精子和不育，证明了SRSF2对睾丸发育和男性生殖至关重要（Xie et al., 2023）。
代谢发育、疾病机制及治疗领域：李向东课题组利用TCGA数据库和临床大样本，发现了环状RNA-circZKSCAN1可编码一个全新的多肽，并且是肝癌患者的潜在诊断标志物。研究揭示了该多肽通过促进FBXW7与mTOR的互作，从而促进mTOR泛素化，最终抑制肝癌恶性进展的分子机理。该发现表明环状RNA 编码的多肽-circZKSaa有潜力作为肝细胞癌的临床诊断标志物和治疗靶点（Song et al., 2023）。陈忠周课题组揭示了TR4对底物的选择机制以及TR4活性的抑制机制。此外，陈忠周课题组还利用小角散射实验确定了复合物在溶液中的聚集状态；利用双荧光素酶报告基因实验确定了TR4和JAZF1在体内的关键致癌位点信息。这些结构信息和体内外的实验结果将有助于更好地理解TR4在癌症和糖脂代谢异常等疾病中发挥作用的机理以及推进针对TR4抗病药物的研发（Liu et al., 2023）。孟庆勇课题组揭示了肌肉卫星细胞中IL34的敲除通过激活NF-κB信号促进Igfbp5的转录，进而下调AKT的磷酸化，最终导致卫星细胞分化障碍。此外，敲除mdx小鼠的IL34、干扰mdx小鼠的AKT活性以及增强mdx小鼠骨骼肌的IGFBP5功能均可改善杜氏骨骼肌营养不良表型（Su et al., 2023）。刘维全课题组和田杰生课题组通过将重组亲和体支架连接到磁小体避免靶向药物递送的蛋白质电晕现象，提高了纳米颗粒在模拟体内环境中的靶向和药物递送能力（Ma et al., 2022）。
代表性论文：
1. Niu, S., Cheng, K., Jia, L., Liang, J., Mu, L., Wang, Y., Yang, X., Yang, C., Zhang, Y., Wang, C., Huang, L., Wang, H., Zhang, S., &Zhang, H. (2023). Lineage tracing of mutant granulosa cells reveals in vivo protective mechanisms that prevent granulosa cell tumorigenesis. Cell Death Differ, 30(5), 1235-1246.
2. Mu, L., & Zhang, H. (2022). Female fertility: The role of mitochondrial protease LONP1 in oocyte development and survival. EBioMedicine, 77, 103881.
3. Zhou, J., Lin, L., Cai, H., Liu, L., Wang, H., Zhang, J., Xia, G., Wang, J., Wang, F., &Wang, C. (2023). SP1 impacts the primordial to primary follicle transition by regulating cholesterol metabolism in granulosa cells. FASEB J, 37(2), e22767.
4. Zhu, Z., Qin, S., Zhang, T., He, M., Zheng, W., Zhao, T., Gao, M., Chen, Z., Zhou, B., Xia, G., &Wang, C. (2023). Pre-granulosa cell-derived FGF23 protects oocytes from premature apoptosis during primordial follicle formation by inhibiting p38 MAPK in mice. J Biol Chem, 104776.
5. Zhang, L., Liu, K., Zhuan, Q., Liu, Z., Meng, L., Fu, X., Jia, G., &Hou, Y. (2022). Mitochondrial Calcium Disorder Affects Early Embryonic Development in Mice through Regulating the ERK/MAPK Pathway. Oxid Med Cell Longev, 2022, 8221361.
6. Sun, L., Lv, Z., Chen, X., Wang, C., Lv, P., Yan, L., Tian, S., Xie, X., Yao, X., Liu, J., Wang, Z., Luo, H., Cui, S., &Liu, J. (2023). SRSF1 regulates primordial follicle formation and number determination during meiotic prophase I. BMC Biol, 21(1), 49.
7. Xie, X., Sun, L., Duan, Y., Lv, Z., Yao, X., Wang, C., Chen, X., Tian, S., Yan, L., Shao, Y., Luo, H., &Liu, J. (2023). SRSF2 in Sertoli cells is essential for testicular development and spermatogenesis in mice. FASEB J, 37(5), e22918.
8. Wang, Y., Wang, W., Cheng, K., Geng, K., Liang, J., Wang, P., Zhang, J., Niu, S., Jia, L., Zhang, S., Li, L., Feng, X., Wang, C., Wang, H., Zhang, H., &Zhang, Y. (2022). Polycomb subunit Pcgf2 mediates ovulation and fertility through transcriptional regulation progesterone receptor. Front Cell Dev Biol, 10, 1010601.
9. Song R, Ma S, Xu J, Ren X, Guo P, Liu H, Li P, Yin F, Liu M, Wang Q, Yu L, Liu J, Duan B, Rahman NA, Wołczyński S, Li G, Li X. A novel polypeptide encoded by the circular RNA ZKSCAN1 suppresses HCC via degradation of mTOR. Mol Cancer. 2023 Jan 23;22(1):16.
10. Liu, Y., Ma, L., Li, M., Tian, Z., Yang, M., Wu, X., Wang, X., Shang, G., Xie, M., Chen, Y., Liu, X., Jiang, L., Wu, W., Xu, C., Xia, L., Li, G., Dai, S., &Chen, Z. (2023). Structures of human TR4LBD-JAZF1 and TR4DBD-DNA complexes reveal the molecular basis of transcriptional regulation. Nucleic Acids Res, 51, 1443-1457.
11. Su, Y., Cao, Y., Liu, C., Xu, Q., Li, N., Lan, M., Li, L., Wang, K., Zhang, Z., &Meng, Q. (2023). Inactivating IL34 promotes regenerating muscle stem cell expansion and attenuates Duchenne muscular dystrophy in mouse models. Theranostics, 13(8), 2588-2604.
12. Ma, S., Gu, C., Xu, J., He, J., Li, S., Zheng, H., Pang, B., Wen, Y., Fang, Q., Liu, W., &Tian, J. (2022). Strategy for Avoiding Protein Corona Inhibition of Targeted Drug Delivery by Linking Recombinant Affibody Scaffold to Magnetosomes. Int J Nanomedicine, 17, 665-680.
撰稿：孟庆勇
校对：张华
审阅：楼慧强
