Spatial transcriptome of developmental mouse brain reveals temporal dynamics of gene expressions and heterogeneity of the claustrum
Spatial transcriptome of developmental mouse brain reveals temporal dynamics of gene expressions and heterogeneity of the claustrum
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发育小鼠大脑的空间转录组揭示了基因表达的时间动态和屏状体的异质性
DOI：
10.1101/2023.04.12.536360
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Ohtaka-Maruyama Chiaki
中科院分区：
文献类型：
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作者：
Hara Yuichiro;Kumamoto Takuma;Yoshizawa-Sugata Naoko;Hirai Kumiko;Xianghe Song;Kawaji Hideya;Ohtaka-Maruyama Chiaki
在哺乳动物大脑皮层的发育过程中，大量神经元以由内而外的方式排列成六层结构，形成新皮层和神经回路。这个过程包括细胞增殖、分化、迁移和成熟，并有精确的基因调控。为了在细胞和分子水平上理解这一过程序列，有必要通过基因表达来表征基本解剖结构。然而，在成人大脑中建立的标记有时在胎儿大脑中表现不同，在发育过程中积极改变。空间转录组从组织切片上的每个点产生全基因组基因表达谱，从新鲜冷冻切片中捕获RNA分子，并在保留空间信息的同时进行测序分析。然而，对这些数据的更深入理解需要计算估计，包括与单细胞转录组数据的整合和单细胞簇水平上的斑点聚集。这种分析在生物标志物发现中的应用最近才开始，在胎儿大脑发育中的应用在很大程度上还未被探索。在这项研究中，我们对发育中的小鼠大脑进行了空间转录组分析，以研究发育过程中基因表达的时空调控。利用这些数据，我们对公开可用的小鼠数据集、成人大脑的空间转录组和胎儿大脑的单细胞转录组进行了综合研究。我们的数据驱动分析确定了脉络膜丛、梨状皮质、丘脑和屏状体的新分子标记。此外，我们揭示了胚胎屏状体的内部结构是由异质细胞群组成的。
During the development of the mammalian cerebral cortex, numerous neurons are arranged in a six-layer structure with an inside-out fashion to form the neocortex and wire neural circuits. This process includes cell proliferation, differentiation, migration, and maturation, supported by precise genetic regulation. To understand this sequence of processes at the cellular and molecular levels, it is necessary to characterize the fundamental anatomical structures by gene expression. However, markers established in the adult brain sometimes behave differently in the fetal brain, actively changing during development. Spatial transcriptomes yield genome-wide gene expression profiles from each spot patterned on tissue sections, capturing RNA molecules from fresh-frozen sections and enabling sequencing analysis while preserving spatial information. However, a deeper understanding of this data requires computational estimation, including integration with single-cell transcriptome data and aggregation of spots on the single-cell cluster level. The application of such analysis to biomarker discovery has only begun recently, and its application to the developing fetal brain is largely unexplored. In this study, we performed a spatial transcriptome analysis of the developing mouse brain to investigate the spatiotemporal regulation of gene expression during development. Using these data, we conducted an integrated study with publicly available mouse data sets, the adult brain’s spatial transcriptome, and the fetal brain’s single-cell transcriptome. Our data-driven analysis identified novel molecular markers of the choroid plexus, piriform cortex, thalamus, and claustrum. In addition, we revealed that the internal structure of the embryonic claustrum is composed of heterogeneous cell populations.