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Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs. However, cellular and molecular understanding of SARS-CoV-2 infection-associated pathology and immune defense features in different organs remains incomplete. Here, we profiled approximately 77 000 single-nucleus transcriptomes of the lung, liver, kidney, and cerebral cortex in rhesus macaques (新型冠状病毒（SARS-CoV-2）感染可以造成多种临床表现和多种器官的组织损伤。但是对于新冠病毒感染相关的病理和免疫防御特征的细胞和分子水平的理解还不完善。该研究中，我们对感染新冠病毒的猕猴及健康对照个体的肺脏、肝脏、肾脏、大脑皮层进行单细胞核转录组测序和分析，共获得了约77 000个单细胞核的转录组数据。多器官数据集整合分析结果表明肝脏具有最强的全局转录改变。我们发现肺脏中的上皮细胞，尤其是AT2细胞和纤毛细胞，存在突出的损伤特征，在成纤维细胞中纤维化迹象明显。肺部的这些损伤特征与新冠肺炎（COVID-19）病人中报道的结果很相似。此外，我们发现肺中的主要组织相容性复合体（MHC）I/II类分子活性下调，肝脏中存在炎症反应和犬尿氨酸通路的激活，它会诱导免疫抑制性微环境的发展。对肾脏数据集的分析发现肾小管上皮细胞对新冠病毒具有更强的趋向性，同时发现了感染猕猴出现了由足细胞失调引起的膜性肾病(一种自身免疫疾病)。另外，我们还识别到了大脑皮层中星形胶质细胞和少突胶质细胞的病理状态，为新冠肺炎相关的神经学影响提供了分子洞察。总之，此项对新冠病毒感染的猕猴模型多器官进行单细胞核转录组研究的工作拓宽了我们对新冠病毒感染造成的疾病特征和机体抗病毒免疫缺陷的理解，这可能促进新冠肺炎治疗干预手段的开发。.

Whether adult hippocampal neurogenesis (AHN) persists in adult and aged humans continues to be extensively debated. A major question is whether the markers identified in rodents are reliable enough to reveal new neurons and the neurogenic trajectory in primates. Here, to provide a better understanding of AHN in primates and to reveal more novel markers for distinct cell types, droplet-based single-nucleus RNA sequencing (snRNA-seq) is used to investigate the cellular heterogeneity and molecular characteristics of the hippocampi in macaques across the lifespan and in aged humans. All of the major cell types in the hippocampus and their expression profiles were identified. The dynamics of the neurogenic lineage was revealed and the diversity of astrocytes and microglia was delineated. In the neurogenic lineage, the regulatory continuum from adult neural stem cells (NSCs) to immature and mature granule cells was investigated. A group of primate-specific markers were identified. We validated ETNPPL as a primate-specific NSC marker and verified STMN1 and STMN2 as immature neuron markers in primates. Furthermore, we illustrate a cluster of active astrocytes and microglia exhibiting proinflammatory responses in aged samples. The interaction analysis and the comparative investigation on published datasets and ours imply that astrocytes provide signals inducing the proliferation, quiescence and inflammation of adult NSCs at different stages and that the proinflammatory status of astrocytes probably contributes to the decrease and variability of AHN in adults and elderly individuals.

Genetic variation confers susceptibility to neurodevelopmental disorders by affecting the development of specific cell types. Changes in cortical and striatal g-aminobutyric acid–expressing (GABAergic) neurons are common in autism and schizophrenia. In this study, we used single-cell RNA sequencing to characterize the emergence of cell diversity in the human ganglionic eminences, the transitory structures of the human fetal brain where striatal and cortical GABAergic neurons are generated. We identified regional and temporal diversity among progenitor cells underlying the generation of a variety of projection neurons and interneurons. We found that these cells are specified within the human ganglionic eminences by transcriptional programs similar to those previously identified in rodents. Our findings reveal an evolutionarily conserved regulatory logic controlling the specification, migration, and differentiation of GABAergic neurons in the human telencephalon.

The hypothalamus comprises various nuclei and neuronal subpopulations that control fundamental homeostasis and behaviors. However, spatiotemporal molecular characterization of hypothalamus development in humans is largely unexplored. Here, we revealed spatiotemporal transcriptome profiles and cell-type characteristics of human hypothalamus development and illustrated the molecular diversity of neural progenitors and the cell-fate decision, which is programmed by a combination of transcription factors. Different neuronal and glial fates are sequentially produced and showed spatial developmental asynchrony. Moreover, human hypothalamic gliogenesis occurs at an earlier stage of gestation and displays distinctive transcription profiles compared with those in mouse. Notably, early oligodendrocyte cells in humans exhibit different gene patterns and interact with neuronal cells to regulate neuronal maturation by Wnt, Hippo, and integrin signals. Overall, our study provides a comprehensive molecular landscape of human hypothalamus development at early- and mid-embryonic stages and a foundation for understanding its spatial and functional complexity.