Molecular features driving cellular complexity of human brain evolution
Molecular features driving cellular complexity of human brain evolution
复制标题
DOI：
10.1038/s41586-023-06338-4
复制
发表时间：
2023-07-19
期刊：
影响因子：
64.8
通讯作者：
Konopka, Genevieve
中科院分区：
文献类型：
--
作者：
Caglayan, Emre;Ayhan, Fatma;Konopka, Genevieve
人类特有的基因组变化促成了人类大脑的独特功能（1 - 5）。人类大脑的细胞异质性（6,7）以及基因表达的复杂调控，凸显了在细胞分辨率下描述人类特有分子特征的必要性。在此，我们分析了来自后扣带回皮质的人类、黑猩猩和恒河猴脑组织的单核RNA测序以及转座酶可及染色质的单核分析测序数据集。我们发现，在整个皮质组织中，少突胶质前体细胞在人类中特异性增加，而成熟少突胶质细胞则减少。少突胶质前体细胞中人类特异性的调控变化加速，并且我们强调了可能与比例变化相关的关键生物学途径。我们还在神经元亚型中确定了人类特异性的调控变化，这揭示了FOXP2仅在两种神经元亚型中在人类中特异性上调。我们还确定了数百个新的人类加速基因组区域，这些区域与人类特异性的染色质可及性变化相关。我们的数据还显示，FOS::JUN和FOX基序在兴奋性神经元亚型的人类特异性可及染色质区域中富集。总之，我们的结果揭示了在细胞类型分辨率下人类大脑进化创新的几种新机制。
Human-specific genomic changes contribute to the unique functionalities of the human brain(1-5). The cellular heterogeneity of the human brain(6,7) and the complex regulation of gene expression highlight the need to characterize human-specific molecular features at cellular resolution. Here we analysed single-nucleus RNA-sequencing and single-nucleus assay for transposase-accessible chromatin with sequencing datasets for human, chimpanzee and rhesus macaque brain tissue from posterior cingulate cortex. We show a human-specific increase of oligodendrocyte progenitor cells and a decrease of mature oligodendrocytes across cortical tissues. Human-specific regulatory changes were accelerated in oligodendrocyte progenitor cells, and we highlight key biological pathways that may be associated with the proportional changes. We also identify human-specific regulatory changes in neuronal subtypes, which reveal human-specific upregulation of FOXP2 in only two of the neuronal subtypes. We additionally identify hundreds of new human accelerated genomic regions associated with human-specific chromatin accessibility changes. Our data also reveal that FOS::JUN and FOX motifs are enriched in the human-specifically accessible chromatin regions of excitatory neuronal subtypes. Together, our results reveal several new mechanisms underlying the evolutionary innovation of human brain at cell-type resolution.