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我们的人体中存在多种类型的干细胞，在机体组织受损、疾病或衰老时这些干细胞就会再生细胞。近日，在一项刊登在国际学术期刊Stem Cell Reports上的研究报告中，来自罗格斯大学的科学家们鉴别出了一种新型因子，其对于维持肠道和大脑干细胞功能非常重要，该因子的缺失会诱发焦虑、认知障碍甚至胃肠道疾病。 该研究揭示了胰岛素样生长因子II（insulin-like growth factor II，IGF-II）基因在大脑和肠道中成体干细胞维持上的重要性。该基因能为肠道中两类功能不同的干细胞提供关键的支持，其不受调节的自我更新和增殖则会引发结直肠癌。IGF-II对于多种类型的成体干细胞非常重要，包括一些对认知功能、嗅觉及组织更新非常关键的成体干细胞。当研究人员在5天内迅速敲除成年小鼠IGF-II基因或者在15天内缓慢敲除成年小鼠IGF-II基因，结果显示，在肠道中快速剔除该基因会导致能够补充肠道内壁组织的干细胞快速缺失，最终使小鼠在一周内体重快速下降并死亡；而缓慢剔除该基因则会使得小鼠通过招募第二种并不活跃的肠道干细胞来维持其生存。研究人员Teresa Wood认为，当IGF-II基因被快速移除后，小肠内壁腺体中的干细胞并不会持续维持细胞替代物的更新，从而引发器官衰竭，而当该基因被缓慢移除后，就能给其它干细胞接替丢失干细胞生物功能的时间和机会。 这项研究首次指出了IGF-II基因在维持成体干细胞功能中的作用，为恢复及维持疾病相关大脑和肠道中的成体干细胞功能紊乱提供了新的思路。 推荐阅读原文： Insulin-like growth factor II: an essential adult stem cell niche constituent in brain and intestine. Tissue-specific stem cells have unique properties and growth requirements, but a small set of juxtacrine and paracrine signals have been identified that are required across multiple niches. Whereas insulin-like growth factor II (IGF-II) is necessary for prenatal growth, its role in adult stem cell physiology is largely unknown. We show that loss of Igf2 in adult mice resulted in a ~50% reduction in slowly dividing, label-retaining cells in the two regions of the brain that harbor neural stem cells. Concordantly, induced Igf2 deletion increased newly generated neurons in the olfactory bulb accompanied by hyposmia, and caused impairments in learning and memory and increased anxiety. Induced Igf2 deletion also resulted in rapid loss of stem and progenitor cells in the crypts of Lieberkühn, leading to body-weight loss and lethality and the inability to produce organoids in vitro. These data demonstrate that IGF-II is critical for multiple adult stem cell niches. |
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