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1.
Nature ; 604(7907): 723-731, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35418686

RESUMO

Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.


Assuntos
Macaca fascicularis , Transcriptoma , Animais , Comunicação Celular , Macaca fascicularis/genética , Receptores Virais/genética , Transcriptoma/genética , Via de Sinalização Wnt
2.
iScience ; 27(2): 109009, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38333704

RESUMO

The avian optic tectum (OT) has been studied for its diverse functions, yet a comprehensive molecular landscape at the cellular level has been lacking. In this study, we applied spatial transcriptome sequencing and single-nucleus RNA sequencing (snRNA-seq) to explore the cellular organization and molecular characteristics of the avian OT from two species: Columba livia and Taeniopygia guttata. We identified precise layer structures and provided comprehensive layer-specific signatures of avian OT. Furthermore, we elucidated diverse functions in different layers, with the stratum griseum periventriculare (SGP) potentially playing a key role in advanced functions of OT, like fear response and associative learning. We characterized detailed neuronal subtypes and identified a population of FOXG1+ excitatory neurons, resembling those found in the mouse neocortex, potentially involved in neocortex-related functions and expansion of avian OT. These findings could contribute to our understanding of the architecture of OT, shedding light on visual perception and multifunctional association.

3.
Innovation (Camb) ; 4(1): 100359, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36506806

RESUMO

The BBIBP-CorV severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccine has been authorized for emergency use and widely distributed. We used single-cell transcriptome sequencing to characterize the dynamics of immune responses to the BBIBP-CorV inactivated vaccine. In addition to the expected induction of humoral immunity, we found that the inactivated vaccine induced multiple, comprehensive immune responses, including significantly increased proportions of CD16+ monocytes and activation of monocyte antigen presentation pathways; T cell activation pathway upregulation in CD8+ T cells, along with increased activation of CD4+ T cells; significant enhancement of cell-cell communications between innate and adaptive immunity; and the induction of regulatory CD4+ T cells and co-inhibitory interactions to maintain immune homeostasis after vaccination. Additionally, comparative analysis revealed higher neutralizing antibody levels, distinct expansion of naive T cells, a shared increased proportion of regulatory CD4+ T cells, and upregulated expression of functional genes in booster dose recipients with a longer interval after the second vaccination. Our research will support a comprehensive understanding of the systemic immune responses elicited by the BBIBP-CorV inactivated vaccine, which will facilitate the formulation of better vaccination strategies and the design of new vaccines.

4.
Gigascience ; 122022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38091510

RESUMO

BACKGROUND: The basal ganglia are a complex of interconnected subcortical structures located beneath the mammalian cerebral cortex. The degeneration of dopaminergic neurons in the basal ganglia is the primary pathological feature of Parkinson's disease. Due to a lack of integrated analysis of multiomics datasets across multiple basal ganglia brain regions, very little is known about the regulatory mechanisms of this area. FINDINGS: We utilized high-throughput transcriptomic and epigenomic analysis to profile over 270,000 single-nucleus cells to create a cellular atlas of the basal ganglia, characterizing the cellular composition of 4 regions of basal ganglia in adult macaque brain, including the striatum, substantia nigra (SN), globus pallidum, and amygdala. We found a distinct epigenetic regulation on gene expression of neuronal and nonneuronal cells across regions in basal ganglia. We identified a cluster of SN-specific astrocytes associated with neurodegenerative diseases and further explored the conserved and primate-specific transcriptomics in SN cell types across human, macaque, and mouse. Finally, we integrated our epigenetic landscape of basal ganglia cells with human disease heritability and identified a regulatory module consisting of candidate cis-regulatory elements that are specific to medium spiny neurons and associated with schizophrenia. CONCLUSIONS: In general, our macaque basal ganglia atlas provides valuable insights into the comprehensive transcriptome and epigenome of the most important and populous cell populations in the macaque basal ganglia. We have identified 49 cell types based on transcriptomic profiles and 47 cell types based on epigenomic profiles, some of which exhibit region specificity, and characterized the molecular relationships underlying these brain regions.

5.
N Biotechnol ; 59: 44-50, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-32688061

RESUMO

Target capture DNA library preparation methods primarily use the biotin-streptavidin interaction to enrich target DNA, requiring complex operations and a time-consuming workflow with a series of wash steps at regulated temperatures. Here, a new method is presented termed 'hook ligation' for target DNA library preparation, using CircLigase to capture target DNA. The concept was validated by library preparation, sequencing, and acquisition of target DNA fragment information through bioinformatics analysis. An efficient reference point for single-strand DNA ligation to a hook sequence using CircLigase is also provided and it is shown that the efficiency can be influenced by the length and the position of the complementary area on the target DNA.


Assuntos
Biologia Computacional , DNA Ligases/metabolismo , DNA/genética , Sequenciamento de Nucleotídeos em Larga Escala , Análise de Sequência de DNA , Biotecnologia , DNA/metabolismo , Biblioteca Gênica
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