美国加利福尼亚大学Corey C. Harwell团队取得一项新突破。他们研究出小鼠鼻中隔的星形胶质细胞规格是由发育起源和局部信号共同决定的。这一研究成果于2025年7月28日发表在国际顶尖学术期刊《自然—神经科学》上。

本研究表明，来自表达Nkx2.1-和zic4祖细胞区的无主题间隔星形胶质细胞主要分别分布于间隔内侧核和间隔外侧核。这些区域的星形胶质细胞表现出独特的分子和形态特征。利用单核RNA测序，小组追踪了中隔细胞的发育轨迹，发现神经元和星形胶质细胞经历了区域特异性和发育阶段特异性的局部细胞-细胞相互作用。内间隔和外侧间隔神经元分别表达音猬因子和成纤维细胞生长因子，促进各区域星形胶质细胞的特化。最后，异位细胞移植研究表明，鼻中隔星形胶质细胞规格取决于局部微环境，而与发育起源无关。他们的数据强调了局部环境在决定星形胶质细胞功能特化中的重要性。

据悉，星形胶质细胞在发育过程中受到内在和外在因素的影响，但每种因素的确切作用仍然知之甚少。

附：英文原文

Title: Astrocyte specification in the mouse septum is shaped by both developmental origin and local signals

Author: Xie, Yajun, Reid, Christopher M., Turrero Garca, Miguel, Dale-Huang, Fiona, Granados, Alejandro A., Lu, Yi, Li, Jiwen, Hanson, Sarah M., Mancia Leon, Walter R., Liu, Jonathan, Adam, Manal, Mosto, Olivia, Pisco, Angela O., Zhang, Ye, Alvarez-Buylla, Arturo, Harwell, Corey C.

Issue&Volume: 2025-07-28

Abstract: Astrocyte specification during development is influenced by both intrinsic and extrinsic factors, but the precise contribution of each remains poorly understood. Here we show that mouse septal astrocytes derived from Nkx2.1- and Zic4-expressing progenitor zones are primarily allocated into the medial septal and lateral septal nuclei, respectively. Astrocytes in these areas exhibit distinctive molecular and morphological features. Using single-nucleus RNA sequencing, we traced the developmental trajectories of cells in the septum and found that neurons and astrocytes undergo region-specific and developmental-stage-specific local cell–cell interactions. Expression of the morphogens sonic hedgehog and fibroblast growth factors by medial septal and lateral septal neurons, respectively, promote the specification of astrocytes in each region. Finally, heterotopic cell transplantation studies showed that septal astrocyte specification depends on the local microenvironment, regardless of developmental origin. Our data highlight the importance of the local environment in determining astrocyte functional specialization.

DOI: 10.1038/s41593-025-02007-z

Source: https://www.nature.com/articles/s41593-025-02007-z