填补缝隙:神经干细胞帮助维持它们的微环境
![Neural stem cells (NSCs) produce neurons and glial cells (astrocytes and oligodendrocytes), which are major cells in the brain. NSCs are maintained and expanded by self-renewal in order to avoid depletion during neurogenesis and astrogliogenesis. During midgestation, NSCs reside under hypoxia partly due to immature vasculature. The mechanisms by which NSCs efficiently self-renew under such circumstances have not fully been discovered. To tackle these problems, we first isolated NSCs from midgestation mouse brains and cultured them under the hypoxic condition. Neurosphere formation under the hypoxic condition was dramatically increased compared that under the normoxic condition. Since neurosphere formation is a good indicator of the presence of NSCs, this result suggests a mechanism to maintain NSCs under hypoxia. Our further study surprisingly showed that NSCs cultured under hypoxia secreted vascular endothelial growth factor A (VEGF-A) and its amount was sufficient to induce NSC self-renewal. The experiments such as that using a VEGF-A inhibitor suggest that VEGF-A secreted from NSCs under the hypoxia promotes NSC self-renew and contributes to maintenance and expansion of NSCs. Our results suggest that NSCs have adaptive potential to respond to hypoxia to organize self-advantageous niche involving VEGF-A when the vascular system is immature. This study will help to elucidate mechanisms underlying not only NSC maintenance but also vascular formation in the brain at the embryonic stages since VEGF-A is an important factor for vasculature development. Credit: Department of Stem Cell Regulation, TMDU 填补缝隙:神经干细胞帮助维持它们的微环境](https://scx1.b-cdn.net/csz/news/800a/2023/filling-a-niche-neural.jpg)
当谈到细胞类型时,干细胞有无限的潜力。这些自我更新的细胞,能够在体内产生任何类型的细胞,居住在被称为生态位的特殊微环境中。现在,日本的研究人员对神经干细胞生态位的动态有了新的认识,神经干细胞生态位是大脑中干细胞的家园。
一项新的研究发表在炎症和再生来自东京医科和牙科大学(TMDU)的研究人员调查了缺氧(低氧)条件对发育过程中神经干细胞生态位的影响。
神经干和祖细胞(NPSCs)产生大脑和神经系统的细胞。已知NSPCs存在于缺氧的生态位中,这意味着生态位中的氧水平低于周围组织的氧水平。然而,这个生态位的组成,以及NSPCs如何在这个生态位中维持自身,尚不完全清楚。
tmdu领导的研究小组开始研究低氧条件对神经干细胞生态位的影响,使用从胚胎小鼠前脑分离的NSPCs细胞培养模型。他们在低氧和正常氧条件下将这些细胞培养成神经球,或自由漂浮的干细胞簇。
该研究的共同主要作者taiichi Kashiwagi说:“结果是惊人的,与常氧条件相比,在低氧条件下观察到神经球的形成显著增加。”“这促使我们探索在缺氧条件下,什么因素在nspc的维持和增殖中发挥作用。”
研究人员评估了一种叫做血管内皮生长因子-A (VEGF-A)作为潜在的候选人。当研究小组将VEGF-A添加到NSPC培养物中时,神经球的形成显著增加。相反,在低氧条件下,用药物抑制剂阻断VEGF-A可以减少神经球形成的增加。此外,在低氧条件下,VEGF-A在nspc中的表达上调。
资深作者Tetsuya Taga说:“我们发现用VEGF-A处理的nspc显示出较低的细胞死亡率和增加的细胞增殖。”“VEGF-A是一个似乎有助于NSPC维护的因素低氧条件。”
这些发现表明NSPCs在缺氧条件下通过VEGF-A的释放来帮助维持其自身的种群。虽然其他因素也可能有助于NSPC的维持,但这些结果揭示了发育过程中神经干细胞生态位的组成,并可能为进一步研究低氧生态位的自组织奠定基础。
更多信息:Taichi Kashiwagi等人,缺氧条件下自分泌VEGF-A发育过程中神经干/祖细胞对自我有利生态位的组织,炎症和再生(2023)。DOI: 10.1186 / s41232 - 022 - 00254 - 2