A Cellular Resolution Spatial Transcriptomic Landscape of the Medial Structures in Postnatal Mouse Brain

Cheng, Mengnan; Wu, Liang; Han, Lei; Huang, Xin; Lai, Yiwei; Xu, Jiangshan; Wang, Shuai; Li, Mei; Zheng, Huiwen; Feng, Weimin; Huang, Zirui; Jiang, Yujia; Hao, Shijie; Li, Zhao; Chen, Xi; Peng, Jian; Guo, Pengcheng; Zhang, Xiao; Lai, Guangyao; Deng, Qiuting; Yuan, Yue; Yang, Fangming; Wei, Xiaoyü; Liao, Sha; Chen, Ao; Volpe, Giacomo; Esteban, Miguel A.; Hou, Yong; Liu, Chuanyu; Liu, Longqi

doi:10.3389/fcell.2022.878346

Cited by 6 publications

(2 citation statements)

References 48 publications

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“…The brain development is governed by sets of genes with distinct spatiotemporal profile. To explore the spatiotemporal dynamics of gene regulation, we collected spatial whole-transcriptome data of developing mouse brain with 7 sagittal sections from embryonic to adult stage (clustered and annotated similarly to coronal sections) (Figure 5A and S6A) including published data on E12.5, E14.5, E16.5 18 and P7 35 mice and newly generated data for P1, P14, and P77 mice. Given that TF regulons, where a core TF dictates a series of downstream genes, are common units for gene regulation, we thus determined spatiotemporal properties of TF regulons.…”

Section: Resultsmentioning

confidence: 99%

Spatially resolved molecular and cellular atlas of the mouse brain

Han,

Liu,

Jing

et al. 2023

Preprint

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A comprehensive atlas of genes, cell types, and their spatial distribution across a whole mammalian brain is fundamental for understanding function of the brain. Here, using snRNA-seq and Stereo-seq techniques, we generated a mouse brain atlas with spatial information for 308 cell clusters with single-cell resolution involving over 6 million cells as well as for 29,655 genes. We have identified new astrocyte clusters, and demonstrated that distinct cell clusters exhibit preference for cortical subregions. In addition, we identified 155 genes exhibiting regional specificity in the brainstem, and 513 long non-coding RNA exhibited regional specificity in the adult brain. Parcellation of brain regions based on spatial transcriptomic information showed large overlap with that by traditional method. Furthermore, we have uncovered 411 transcription factor regulons with spatiotemporal specificity during development. Thus, our study has discovered genes and regulon with spatiotemporal specificity, and provided a high-resolution spatial transcriptomic atlas of the mouse brain.

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Section: Resultsmentioning

confidence: 99%

Spatially resolved molecular and cellular atlas of the mouse brain

Han,

Liu,

Jing

et al. 2023

Preprint

Self Cite

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“…The recently developed Stereo-seq, using the random barcode-labeled DNA nanosphere microarray pattern deposition, presents higher resolution and larger field-of-view than previously reported spatial transcriptomics methods. This method has recently been used to establish spatial and temporal transcriptome profiles of mouse embryos, Drosophila embryos, zebrafish embryos, axolotl brain and Arabidopsis leaves ( Chen et al, 2022a ; Cheng et al, 2022 ; Jiang et al, 2022 ; Liu et al, 2022 ; Wang et al, 2022 ; Xia et al, 2022 ). In this study, we successfully constructed the spatial transcriptome of human placental villi using a modified protocol of Stereo-seq, which provides a valuable resource for future placental researches.…”

Section: Introductionmentioning

confidence: 99%

Resolving the gene expression maps of human first-trimester chorionic villi with spatial transcriptome

Liu

Zhai

Zhang

et al. 2022

Front. Cell Dev. Biol.

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The placenta is important for fetal development in mammals, and spatial transcriptomic profiling of placenta helps to resolve its structure and function. In this study, we described the landscape of spatial transcriptome of human placental villi obtained from two pregnant women at the first trimester using the modified Stereo-seq method applied for paraformaldehyde (PFA) fixation samples. The PFA fixation of human placenta villi was better than fresh villi embedded in optimum cutting temperature (OCT) compound, since it greatly improved tissue morphology and the specificity of RNA signals. The main cell types in chorionic villi such as syncytiotrophoblasts (SCT), villous cytotrophoblasts (VCT), fibroblasts (FB), and extravillous trophoblasts (EVT) were identified with the spatial transcriptome data, whereas the minor cell types of Hofbauer cells (HB) and endothelial cells (Endo) were spatially located by deconvolution of scRNA-seq data. We demonstrated that the Stereo-seq data of human villi could be used for sophisticated analyses such as spatial cell-communication and regulatory activity. We found that the SCT and VCT exhibited the most ligand-receptor pairs that could increase differentiation of the SCT, and that the spatial localization of specific regulons in different cell types was associated with the pathways related to hormones transport and secretion, regulation of mitotic cell cycle, and nutrient transport pathway in SCT. In EVT, regulatory pathways such as the epithelial to mesenchyme transition, epithelial development and differentiation, and extracellular matrix organization were identified. Finally, viral receptors and drug transporters were identified in villi according to the pathway analysis, which could help to explain the vertical transmission of several infectious diseases and drug metabolism efficacy. Our study provides a valuable resource for further investigation of the placenta development, physiology and pathology in a spatial context.

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