The spatiotemporal dynamics of spatially variable genes in developing mouse brain revealed by a novel computational scheme.
The spatiotemporal dynamics of spatially variable genes in developing mouse brain revealed by a novel computational scheme.
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DOI：
10.1038/s41420-023-01569-w
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发表时间：
2023-07-27
影响因子：
7
通讯作者：
Peng, Cheng
中科院分区：
文献类型：
--
作者：
Hong, Yingzhou;Song, Kai;Zhang, Zongbo;Deng, Yuxia;Zhang, Xue;Zhao, Jinqian;Jiang, Jun;Zhang, Qing;Guo, Chunming;Peng, Cheng
为了了解大脑区域是如何形成和工作的，重要的是探索在发育过程中特定大脑区域丰富的空间可变基因(SVG)。空间转录学技术为高通量筛选SVG提供了机会。然而，以往的方法忽略了支持向量机的排序顺序和组合效应，难以从空间转录数据中自动选择高优先级的支持向量机。在这里，我们提出了一种新的计算流水线，称为SVGbit，用于对单个SVG和组合SVG进行排序，用于在不同大脑区域进行标记选择，并在不同类型的公开数据集中进行了测试，包括人和小鼠的大脑。然后，我们生成了小鼠胚胎和新生儿关键阶段大脑的空间转录和免疫组织化学数据。结果表明，我们的排序和聚类方案捕获了关键的SVG，这些关键SVG与小鼠大脑发育中的已知解剖区域一致。更重要的是，SVGbit可以方便地识别不同脑区的多个基因组合集。通过Sox2和Calb2的染色，我们在丘脑中发现了三个动态亚区，并发现在发育过程中，Nr4a2的表达逐渐隔离了新皮质和海马区。综上所述，我们的工作不仅揭示了单个SVG和组合SVG在小鼠大脑发育过程中的时空动态，而且为从空间转录数据中筛选标记基因提供了一条新的计算管道。
To understand how brain regions form and work, it is important to explore the spatially variable genes (SVGs) enriched in specific brain regions during development. Spatial transcriptomics techniques provide opportunity to select SVGs in the high-throughput way. However, previous methods neglected the ranking order and combinatorial effect of SVGs, making them difficult to automatically select the high-priority SVGs from spatial transcriptomics data. Here, we proposed a novel computational pipeline, called SVGbit, to rank the individual and combinatorial SVGs for marker selection in various brain regions, which was tested in different kinds of public datasets for both human and mouse brains. We then generated the spatial transcriptomics and immunohistochemistry data from mouse brain at critical embryonic and neonatal stages. The results show that our ranking and clustering scheme captures the key SVGs which coincide with known anatomic regions in the developing mouse brain. More importantly, SVGbit can facilitate the identification of multiple gene combination sets in different brain regions. We identified three dynamical sub-regions which can be segregated by the staining of Sox2 and Calb2 in thalamus, and we also found that Nr4a2 expression gradually segregates the neocortex and hippocampus during the development. In summary, our work not only reveals the spatiotemporal dynamics of individual and combinatorial SVGs in developing mouse brain, but also provides a novel computational pipeline to facilitate the selection of marker genes from spatial transcriptomics data.
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影响因子：
16.2
作者：
Cargnin F;Kwon JS;Katzman S;Chen B;Lee JW;Lee SK
通讯作者：
Lee SK
影响因子：
25
作者：
Maynard KR;Collado-Torres L;Weber LM;Uytingco C;Barry BK;Williams SR;Catallini JL 2nd;Tran MN;Besich Z;Tippani M;Chew J;Yin Y;Kleinman JE;Hyde TM;Rao N;Hicks SC;Martinowich K;Jaffe AE
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影响因子：
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影响因子：
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作者：
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通讯作者：
Li, James Y. H.
影响因子：
3.6
作者：
ANSELIN, L
通讯作者：
ANSELIN, L