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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.
Nat Commun ; 15(1): 7806, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39242563

RESUMO

Three-dimensional Spatial Transcriptomics has revolutionized our understanding of tissue regionalization, organogenesis, and development. However, existing approaches overlook either spatial information or experiment-induced distortions, leading to significant discrepancies between reconstruction results and in vivo cell locations, causing unreliable downstream analysis. To address these challenges, we propose ST-GEARS (Spatial Transcriptomics GEospatial profile recovery system through AnchoRS). By employing innovative Distributive Constraints into the Optimization scheme, ST-GEARS retrieves anchors with exceeding precision that connect closest spots across sections in vivo. Guided by the anchors, it first rigidly aligns sections, next solves and denoises Elastic Fields to counteract distortions. Through mathematically proved Bi-sectional Fields Application, it eventually recovers the original spatial profile. Studying ST-GEARS across number of sections, sectional distances and sequencing platforms, we observed its outstanding performance on tissue, cell, and gene levels. ST-GEARS provides precise and well-explainable 'gears' between in vivo situations and in vitro analysis, powerfully fueling potential of biological discoveries.


Assuntos
Transcriptoma , Animais , Imageamento Tridimensional/métodos , Camundongos , Perfilação da Expressão Gênica/métodos , Humanos , Algoritmos
3.
Cell Discov ; 10(1): 22, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409116

RESUMO

Human cerebellum encompasses numerous neurons, exhibiting a distinct developmental paradigm from cerebrum. Here we conducted scRNA-seq, scATAC-seq and spatial transcriptomic analyses of fetal samples from gestational week (GW) 13 to 18 to explore the emergence of cellular diversity and developmental programs in the developing human cerebellum. We identified transitory granule cell progenitors that are conserved across species. Special patterns in both granule cells and Purkinje cells were dissected multidimensionally. Species-specific gene expression patterns of cerebellar lobes were characterized and we found that PARM1 exhibited inconsistent distribution in human and mouse granule cells. A novel cluster of potential neuroepithelium at the rhombic lip was identified. We also resolved various subtypes of Purkinje cells and unipolar brush cells and revealed gene regulatory networks controlling their diversification. Therefore, our study offers a valuable multi-omics landscape of human fetal cerebellum and advances our understanding of development and spatial organization of human cerebellum.

4.
iScience ; 25(3): 103857, 2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35198910

RESUMO

Hepatocellular carcinoma (HCC) is the most common liver cancer with a high rate of metastasis. However, the molecular mechanisms that drive metastasis remain unclear. We combined single-cell transcriptomic, proteomic, and chromatin accessibility data to investigate how heterogeneous phenotypes contribute to metastatic potential in five HCC cell lines. We confirmed that the prevalence of a mesenchymal state and levels of cell proliferation are linked to the metastatic potential. We also identified a rare hypoxic subtype that has a higher capacity for glycolysis and exhibits dormant, invasive, and malignant characteristics. This subtype has increased metastatic potential. We further identified a robust 14-gene panel representing this hypoxia signature and this hypoxia signature could serve as a prognostic index. Our data provide a valuable data resource, facilitate a deeper understanding of metastatic mechanisms, and may help diagnosis of metastatic potential in individual patients, thus supporting personalized medicine.

5.
Cell Res ; 32(5): 425-436, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35273378

RESUMO

The differences in size and function between primate and rodent brains, and the association of disturbed excitatory/inhibitory balance with many neurodevelopmental disorders highlight the importance to study primate ganglionic eminences (GEs) development. Here we used single-cell RNA and ATAC sequencing to characterize the emergence of cell diversity in monkey and human GEs where most striatal and cortical interneurons are generated. We identified regional and temporal diversity among progenitor cells which give rise to a variety of interneurons. These cells are specified within the primate GEs by well conserved gene regulatory networks, similar to those identified in mice. However, we detected, in human, several novel regulatory pathways or factors involved in the specification and migration of interneurons. Importantly, comparison of progenitors between our human and published mouse GE datasets led to the discovery and confirmation of outer radial glial cells in GEs in human cortex. Our findings reveal both evolutionarily conservative and nonconservative regulatory networks in primate GEs, which may contribute to their larger brain sizes and more complex neural networks compared with mouse.


Assuntos
Interneurônios , RNA , Animais , Encéfalo , Diferenciação Celular/fisiologia , Córtex Cerebral , Interneurônios/metabolismo , Camundongos , Primatas , RNA/metabolismo
6.
Nat Commun ; 13(1): 6747, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36347848

RESUMO

Single cell approaches have increased our knowledge about the cell type composition of the non-human primate (NHP), but a detailed characterization of area-specific regulatory features remains outstanding. We generated single-cell transcriptomic and chromatin accessibility (single-cell ATAC) data of 358,237 cells from prefrontal cortex (PFC), primary motor cortex (M1) and primary visual cortex (V1) of adult female cynomolgus monkey brain, and integrated this dataset with Stereo-seq (spatial enhanced resolution omics-sequencing) of the corresponding cortical areas to assign topographic information to molecular states. We identified area-specific chromatin accessible sites and their targeted genes, including the cell type-specific transcriptional regulatory network associated with excitatory neurons heterogeneity. We reveal calcium ion transport and axon guidance genes related to specialized functions of PFC and M1, identified the similarities and differences between adult macaque and human oligodendrocyte trajectories, and mapped the genetic variants and gene perturbations of human diseases to NHP cortical cells. This resource establishes a transcriptomic and chromatin accessibility combinatory regulatory landscape at a single-cell and spatially resolved resolution in NHP cortex.


Assuntos
Neurônios , Córtex Pré-Frontal , Animais , Feminino , Macaca fascicularis/genética , Neurônios/metabolismo , Córtex Pré-Frontal/metabolismo , Redes Reguladoras de Genes , Cromatina/genética , Cromatina/metabolismo
7.
Materials (Basel) ; 14(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34361366

RESUMO

Selective laser melting (SLM) is a forming technology in the field of metal additive manufacturing. In order to improve the quality of formed parts, it is necessary to monitor the selective laser melting forming process. At present, most of the research on the monitoring of the selective laser melting forming process focuses on the monitoring of the melting pool, but the quality of forming parts cannot be controlled in real-time. As an indispensable link in the SLM forming process, the quality of powder spreading directly affects the quality of the formed parts. Therefore, this paper proposes a detection method for SLM powder spreading defects, mainly using industrial cameras to collect SLM powder spreading surfaces, designing corresponding image processing algorithms to extract three common powder spreading defects, and establishing appropriate classifiers to distinguish different types of powder spreading defects. It is determined that the multilayer perceptron (MLP) is the most accurate classifier. This detection method has high recognition rate and fast detection speed, which cannot only meet the SLM forming efficiency, but also improve the quality of the formed parts through feedback control.

8.
Front Public Health ; 8: 581088, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33569367

RESUMO

Online depression communities offer people with depressed symptoms new opportunities to obtain health information and provide social support for each other to fight against the depression. We sought to investigate whether usage of online community help improve depression outcomes and determine which types of usage behaviors have positive or negative effects on depression. We proposed that two dimensions of the sense of belonging (sense of identity and trust) and three dimensions of the sense of support (informational, emotional, and socializing) have significant effects on depression, and further considered gender difference and its effect on depression. We obtained a dataset consisting of 465,337 posts from 244 members from a popular online depression community to test all 10 proposed hypotheses. The results reveal that (i) the sense of shared identity, trust, informational support, and emotional support have positive effects on depression, while socializing support have negative effects on depression, and (ii) the sense of shared identity and trust have more positive effects on depression for female users than male users while socializing support has a more negative effect on depression for female users than for male users. The findings have important practical implications for designers and managers of online depression communities.


Assuntos
Mídias Sociais , Depressão/terapia , Emoções , Feminino , Humanos , Masculino , Saúde Mental , Apoio Social
9.
Sci Rep ; 10(1): 18863, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33139759

RESUMO

Recent studies show that non-coding RNAs (ncRNAs) can regulate the expression of protein-coding genes and play important roles in mammalian development. Previous studies have revealed that during C. elegans (Caenorhabditis elegans) embryo development, numerous genes in each cell are spatiotemporally regulated, causing the cell to differentiate into distinct cell types and tissues. We ask whether ncRNAs participate in the spatiotemporal regulation of genes in different types of cells and tissues during the embryogenesis of C. elegans. Here, by using marker-free full-length high-depth single-cell RNA sequencing (scRNA-seq) technique, we sequence the whole transcriptomes from 1031 embryonic cells of C. elegans and detect 20,431 protein-coding genes, including 22 cell-type-specific protein-coding markers, and 9843 ncRNAs including 11 cell-type-specific ncRNA markers. We induce a ncRNAs-based clustering strategy as a complementary strategy to the protein-coding gene-based clustering strategy for single-cell classification. We identify 94 ncRNAs that have never been reported to regulate gene expressions, are co-expressed with 1208 protein-coding genes in cell type specific and/or embryo time specific manners. Our findings suggest that these ncRNAs could potentially influence the spatiotemporal expression of the corresponding genes during the embryogenesis of C. elegans.


Assuntos
Caenorhabditis elegans/genética , Desenvolvimento Embrionário/genética , RNA não Traduzido/genética , Transcriptoma/genética , Animais , Caenorhabditis elegans/crescimento & desenvolvimento , Proteínas de Caenorhabditis elegans/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , RNA não Traduzido/classificação , Análise de Célula Única
10.
Healthcare (Basel) ; 7(4)2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31689952

RESUMO

Online depression communities give people additional opportunities to share their experiences and exchange social support to care for themselves in fighting against depression. We aimed to explore what drives patients to share in online depression communities. We used three dimensions of social capital (structural, relational, and cognitive) to explain their sharing behaviors. We further proposed that five factors (social interaction ties, a sense of shared identity, trust, expertise, and a sense of shared values) will have significant, positive effects on sharing behaviors and that there are differences among patients who have spent different lengths of time participating in online depression communities. We then chose a popular online depression community in China as our data source and obtained a dataset consisting of 31,440 posts from 197 members. Then, we employed panel data regression analyses to test all six hypotheses. The results revealed that all five factors had significant, positive effects (p < 0.01) on patients' sharing behaviors, and the effects were significantly different across groups. Our empirical results help designers and managers of online depression communities take specific measures to facilitate community members' access to social capital resources. Meanwhile, our results have implications for existing health management and e-health literature.

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