瑞士苏黎世大学Sebastian Jessberger研究小组发现，FASN依赖性脂质代谢将神经源性干细胞/祖细胞（NSPC）活动与学习和记忆障碍联系起来。相关论文2020年5月7日在线发表于《细胞—干细胞》。

研究人员探究了小鼠和表达突变脂肪酸合酶（FASN; R1819W）的人类胚胎干细胞（hESCs）中脂质代谢和认知功能之间的联系，FASN是最近在具有智力障碍的人类中发现的啮齿动物NSPC活性的代谢调节剂。

由于NSPC中的脂质蓄积和随后脂肪生成性ER应激，FASN R1812W变体纯合的小鼠损害了成年海马NSPC活性并具有认知缺陷。纯合FASN R1819W hESC来源的NSPCs在胚胎2D培养和3D前脑区域化类器官中的增殖速率降低，与发育表型一致。

这些来自成年小鼠模型和人脑发育体外模型的数据表明，脂质代谢改变会导致智力障碍。

研究人员表示，NSPC活动的改变和神经发育缺陷与智力障碍有关。然而，尚不清楚改变代谢（NSPC活性的关键调节因子）是否会破坏人类神经发生并可能导致认知缺陷。

附：英文原文

Title: FASN-Dependent Lipid Metabolism Links Neurogenic Stem/Progenitor Cell Activity to Learning and Memory Deficits

Author: Megan Bowers, Tong Liang, Daniel Gonzalez-Bohorquez, Sara Zocher, Baptiste N. Jaeger, Werner J. Kovacs, Clemens Rhrl, Kaitlyn M.L. Cramb, Jochen Winterer, Merit Kruse, Slavica Dimitrieva, Rupert W. Overall, Thomas Wegleiter, Hossein Najmabadi, Clay F. Semenkovich, Gerd Kempermann, Csaba Fldy, Sebastian Jessberger

Issue&Volume: 2020-05-07

Abstract: Altered neural stem/progenitor cell (NSPC) activity and neurodevelopmental defectsare linked to intellectual disability. However, it remains unclear whether alteredmetabolism, a key regulator of NSPC activity, disrupts human neurogenesis and potentiallycontributes to cognitive defects. We investigated links between lipid metabolism andcognitive function in mice and human embryonic stem cells (hESCs) expressing mutantfatty acid synthase (FASN; R1819W), a metabolic regulator of rodent NSPC activityrecently identified in humans with intellectual disability. Mice homozygous for theFASN R1812W variant have impaired adult hippocampal NSPC activity and cognitive defectsbecause of lipid accumulation in NSPCs and subsequent lipogenic ER stress. HomozygousFASN R1819W hESC-derived NSPCs show reduced rates of proliferation in embryonic 2Dcultures and 3D forebrain regionalized organoids, consistent with a developmentalphenotype. These data from adult mouse models and in vitro models of human brain development suggest that altered lipid metabolism contributesto intellectual disability.

DOI: 10.1016/j.stem.2020.04.002

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30141-7