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神经胶质细胞铁蛋白通过运输自我更新所需的铁来维持神经干细胞。

Glial ferritin maintains neural stem cells via transporting iron required for self-renewal in .

机构信息

School of Life Science and Technology, Department of Neurosurgery, Zhongda Hospital, The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Southeast University, Nanjing, China.

Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.

出版信息

Elife. 2024 Sep 10;13:RP93604. doi: 10.7554/eLife.93604.

Abstract

Stem cell niche is critical for regulating the behavior of stem cells. neural stem cells (Neuroblasts, NBs) are encased by glial niche cells closely, but it still remains unclear whether glial niche cells can regulate the self-renewal and differentiation of NBs. Here, we show that ferritin produced by glia, cooperates with Zip13 to transport iron into NBs for the energy production, which is essential to the self-renewal and proliferation of NBs. The knockdown of glial ferritin encoding genes causes energy shortage in NBs via downregulating aconitase activity and NAD level, which leads to the low proliferation and premature differentiation of NBs mediated by Prospero entering nuclei. More importantly, ferritin is a potential target for tumor suppression. In addition, the level of glial ferritin production is affected by the status of NBs, establishing a bicellular iron homeostasis. In this study, we demonstrate that glial cells are indispensable to maintain the self-renewal of NBs, unveiling a novel role of the NB glial niche during brain development.

摘要

干细胞龛对于调节干细胞的行为至关重要。神经干细胞(神经母细胞,NBs)被胶质龛细胞紧密包裹,但胶质龛细胞是否能调节 NBs 的自我更新和分化仍不清楚。在这里,我们发现胶质细胞产生的铁蛋白与 Zip13 合作,将铁运输到 NBs 中用于能量产生,这对 NBs 的自我更新和增殖至关重要。胶质铁蛋白编码基因的敲低通过下调柠檬酸合酶活性和 NAD 水平导致 NBs 中的能量短缺,从而导致 Prospero 进入细胞核介导的 NBs 的低增殖和过早分化。更重要的是,铁蛋白是肿瘤抑制的潜在靶点。此外,胶质铁蛋白的产生水平受 NBs 状态的影响,从而建立了双细胞铁稳态。在这项研究中,我们证明了胶质细胞对于维持 NBs 的自我更新是不可或缺的,揭示了 NB 胶质龛在大脑发育过程中的新作用。

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