Temporal and sequential transcriptional dynamics define lineage shifts in corticogenesis.
Temporal and sequential transcriptional dynamics define lineage shifts in corticogenesis.
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DOI：
10.15252/embj.2022111132
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发表时间：
2022-12-15
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影响因子：
--
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中科院分区：
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--
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大脑皮层包含数十亿个神经元，它们的混乱或错误指定会导致神经发育障碍。了解皮质神经干细胞（NSCs）如何产生过多的投射神经元亚型是一个重大挑战。在这里，我们专注于阐明小鼠胚胎神经干细胞，基底祖细胞（BP）和新生神经元（NBNs）在整个皮层发育的转录景观。我们揭示了转录空间随时间的动态变化和每个祖细胞群体内的异质性。我们确定了NSC，BP和NBN簇的签名标志，并预测了有助于神经命运规范的活跃转录节点和网络。我们发现，受体，配体和下游途径的表达是高度动态的，随着时间的推移和整个谱系意味着不同的信号反应。因此，我们提供了皮质发育期间基因表达的广泛概要，这将是研究神经发育过程和神经发育障碍的宝贵资源。发育过程中小鼠大脑皮层细胞转录组图谱揭示了与细胞命运决定相对应的基因表达模式。
The cerebral cortex contains billions of neurons, and their disorganization or misspecification leads to neurodevelopmental disorders. Understanding how the plethora of projection neuron subtypes are generated by cortical neural stem cells (NSCs) is a major challenge. Here, we focused on elucidating the transcriptional landscape of murine embryonic NSCs, basal progenitors (BPs), and newborn neurons (NBNs) throughout cortical development. We uncover dynamic shifts in transcriptional space over time and heterogeneity within each progenitor population. We identified signature hallmarks of NSC, BP, and NBN clusters and predict active transcriptional nodes and networks that contribute to neural fate specification. We find that the expression of receptors, ligands, and downstream pathway components is highly dynamic over time and throughout the lineage implying differential responsiveness to signals. Thus, we provide an expansive compendium of gene expression during cortical development that will be an invaluable resource for studying neural developmental processes and neurodevelopmental disorders. An atlas of mouse cerebral cortical cell transcriptome during development reveal patterns of gene expression that correspond to cell fate decisions.
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影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
9.2
作者：
Blaschuk, KL;ffrench-Constant, C
通讯作者：
ffrench-Constant, C
影响因子：
10.5
作者：
Arnold, Sebastian J.;Huang, Guo-Jen;Groszer, Matthias
通讯作者：
Groszer, Matthias
影响因子：
4.6
作者：
Bansod, Shama;Kageyama, Ryoichiro;Ohtsuka, Toshiyuki
通讯作者：
Ohtsuka, Toshiyuki