Developmental origin and local signals cooperate to determine septal astrocyte identity.
Developmental origin and local signals cooperate to determine septal astrocyte identity.
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发育起源和局部信号共同确定间隔星形胶质细胞的身份。
DOI：
10.1101/2023.10.08.561428
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Harwell,CoreyC
中科院分区：
文献类型：
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作者：
Xie,Yajun;Reid,ChristopherM;Granados,AlejandroA;Garcia,MiguelTurrero;Dale-Huang,Fiona;Hanson,SarahM;Mancia,Walter;Liu,Jonathan;Adam,Manal;Mosto,Olivia;Pisco,AngelaO;Alvarez-Buylla,Arturo;Harwell,CoreyC
星形胶质细胞在发育过程中的特性既受内在因素的影响，也受外在因素的影响，但每种因素的确切贡献仍然知之甚少。在这里，我们发现Nkx2.1和Zic4的隔区星形胶质细胞分别被分配到内侧隔核(MS)和外侧隔核(LS)的非重叠区域。这些区域的星形胶质细胞表现出独特的分子和形态特征，适合每个核独特的细胞和突触电路环境。利用单核(Sn)RNA测序，我们追踪了隔区细胞的发育轨迹，发现神经元和星形胶质细胞经历了区域和发育阶段特定的局部细胞-细胞相互作用。我们发现MS和LS神经元分别表达经典的形态因子Sonic hedgehog(Shh)和成纤维细胞生长因子(FGFs)，促进每个区域局部星形胶质细胞的分子规格。最后，利用异位细胞移植，我们发现隔区星形胶质细胞的形态和分子特性都高度依赖于局部微环境，而与发育来源无关。我们的数据突出了塑造星形胶质细胞特性的内在和外在因素之间的复杂相互作用，并阐明了局部环境在决定星形胶质细胞功能特化方面的重要性。
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 septal astrocytes from Nkx2.1 and Zic4 expressing progenitor zones are allocated into non-overlapping domains of the medial (MS) and lateral septal nuclei (LS) respectively. Astrocytes in these areas exhibit distinctive molecular and morphological features tailored to the unique cellular and synaptic circuit environment of each nucleus. Using single-nucleus (sn) RNA sequencing, we trace the developmental trajectories of cells in the septum and find that neurons and astrocytes undergo region and developmental stage-specific local cell-cell interactions. We show that expression of the classic morphogens Sonic hedgehog (Shh) and Fibroblast growth factors (Fgfs) by MS and LS neurons respectively, functions to promote the molecular specification of local astrocytes in each region. Finally, using heterotopic cell transplantation, we show that both morphological and molecular specifications of septal astrocytes are highly dependent on the local microenvironment, regardless of developmental origins. Our data highlights the complex interplay between intrinsic and extrinsic factors shaping astrocyte identities and illustrates the importance of the local environment in determining astrocyte functional specialization.