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人类大脑成熟过程中细胞类型特异性基因表达动态

Cell type-specific gene expression dynamics during human brain maturation.

作者信息

Steyn Christina, Mishi Ruvimbo, Fillmore Stephanie, Verhoog Matthijs B, More Jessica, Rohlwink Ursula K, Melvill Roger, Butler James, Enslin Johannes M N, Jacobs Muazzam, Sauka-Spengler Tatjana, Greco Maria, Quiñones Sadi, Dulla Chris G, Raimondo Joseph V, Figaji Anthony, Hockman Dorit

机构信息

Division of Cell Biology, Department of Human Biology, University of Cape Town, Cape Town, South Africa.

Neuroscience Institute, University of Cape Town, Cape Town, South Africa.

出版信息

bioRxiv. 2024 May 17:2023.09.29.560114. doi: 10.1101/2023.09.29.560114.

DOI:10.1101/2023.09.29.560114
PMID:37808657
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10557738/
Abstract

The human brain undergoes protracted post-natal maturation, guided by dynamic changes in gene expression. Most studies exploring these processes have used bulk tissue analyses, which mask cell type-specific gene expression dynamics. Here, using single nucleus (sn)RNA-seq on temporal lobe tissue, including samples of African ancestry, we build a joint paediatric and adult atlas of 75 cell subtypes, which we verify with spatial transcriptomics. We explore the differences between paediatric and adult cell types, revealing the genes and pathways that change during brain maturation. Our results highlight excitatory neuron subtypes, including the and subtypes, that show elevated expression of genes associated with cognition and synaptic plasticity in paediatric tissue. The new resources we present here improve our understanding of the brain during its development and contribute to global efforts to build an inclusive brain cell map.

摘要

人类大脑在出生后经历长期成熟过程,由基因表达的动态变化引导。大多数探索这些过程的研究都使用了大块组织分析,这掩盖了细胞类型特异性的基因表达动态。在这里,我们对颞叶组织(包括非洲血统样本)进行单核(sn)RNA测序,构建了一个包含75种细胞亚型的儿童和成人联合图谱,并通过空间转录组学进行了验证。我们探索了儿童和成人细胞类型之间的差异,揭示了大脑成熟过程中发生变化的基因和通路。我们的结果突出了兴奋性神经元亚型,包括 和 亚型,这些亚型在儿童组织中显示出与认知和突触可塑性相关基因的表达升高。我们在此展示的新资源增进了我们对大脑发育过程的理解,并有助于全球构建包容性脑细胞图谱的努力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f230/11105904/f9c4f00c1beb/nihpp-2023.09.29.560114v2-f0017.jpg
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Genes associated with cognitive ability and HAR show overlapping expression patterns in human cortical neuron types.与认知能力和 HAR 相关的基因在人类皮质神经元类型中表现出重叠的表达模式。
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Decoupling of mRNA and Protein Expression in Aging Brains Reveals the Age-Dependent Adaptation of Specific Gene Subsets.衰老大脑中 mRNA 和蛋白质表达的解偶联揭示了特定基因子集随年龄变化的适应。
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