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1.
Nature ; 590(7846): 457-462, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33568812

RESUMO

In contrast to nearly all other tissues, the anatomy of cell differentiation in the bone marrow remains unknown. This is owing to a lack of strategies for examining myelopoiesis-the differentiation of myeloid progenitors into a large variety of innate immune cells-in situ in the bone marrow. Such strategies are required to understand differentiation and lineage-commitment decisions, and to define how spatial organizing cues inform tissue function. Here we develop approaches for imaging myelopoiesis in mice, and generate atlases showing the differentiation of granulocytes, monocytes and dendritic cells. The generation of granulocytes and dendritic cells-monocytes localizes to different blood-vessel structures known as sinusoids, and displays lineage-specific spatial and clonal architectures. Acute systemic infection with Listeria monocytogenes induces lineage-specific progenitor clusters to undergo increased self-renewal of progenitors, but the different lineages remain spatially separated. Monocyte-dendritic cell progenitors (MDPs) map with nonclassical monocytes and conventional dendritic cells; these localize to a subset of blood vessels expressing a major regulator of myelopoiesis, colony-stimulating factor 1 (CSF1, also known as M-CSF)1. Specific deletion of Csf1 in endothelium disrupts the architecture around MDPs and their localization to sinusoids. Subsequently, there are fewer MDPs and their ability to differentiate is reduced, leading to a loss of nonclassical monocytes and dendritic cells during both homeostasis and infection. These data indicate that local cues produced by distinct blood vessels are responsible for the spatial organization of definitive blood cell differentiation.


Assuntos
Rastreamento de Células/métodos , Células Mieloides/citologia , Mielopoese , Coloração e Rotulagem/métodos , Animais , Atlas como Assunto , Vasos Sanguíneos/citologia , Vasos Sanguíneos/metabolismo , Linhagem da Célula , Autorrenovação Celular , Células Dendríticas/citologia , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Feminino , Granulócitos/citologia , Listeria monocytogenes/patogenicidade , Listeriose/microbiologia , Fator Estimulador de Colônias de Macrófagos/deficiência , Fator Estimulador de Colônias de Macrófagos/genética , Fator Estimulador de Colônias de Macrófagos/metabolismo , Masculino , Camundongos , Monócitos/citologia , Células Mieloides/metabolismo
3.
Science ; 371(6527)2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33479125

RESUMO

The skin confers biophysical and immunological protection through a complex cellular network established early in embryonic development. We profiled the transcriptomes of more than 500,000 single cells from developing human fetal skin, healthy adult skin, and adult skin with atopic dermatitis and psoriasis. We leveraged these datasets to compare cell states across development, homeostasis, and disease. Our analysis revealed an enrichment of innate immune cells in skin during the first trimester and clonal expansion of disease-associated lymphocytes in atopic dermatitis and psoriasis. We uncovered and validated in situ a reemergence of prenatal vascular endothelial cell and macrophage cellular programs in atopic dermatitis and psoriasis lesional skin. These data illustrate the dynamism of cutaneous immunity and provide opportunities for targeting pathological developmental programs in inflammatory skin diseases.


Assuntos
Dermatite Atópica/embriologia , Dermatite Atópica/patologia , Psoríase/embriologia , Psoríase/patologia , Pele/embriologia , Animais , Atlas como Assunto , Movimento Celular , Conjuntos de Dados como Assunto , Células Dendríticas/imunologia , Dermatite Atópica/imunologia , Fármacos Dermatológicos/farmacologia , Humanos , Imunidade Inata/genética , Metotrexato/farmacologia , Camundongos , Fagócitos/imunologia , Psoríase/imunologia , Análise de Célula Única , Pele/citologia , Pele/imunologia , Linfócitos T/imunologia , Transcriptoma
4.
PLoS Biol ; 18(12): e3000971, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33383575

RESUMO

Chimpanzees (Pan troglodytes) are, along with bonobos, humans' closest living relatives. The advent of diffusion MRI tractography in recent years has allowed a resurgence of comparative neuroanatomical studies in humans and other primate species. Here we offer, in comparative perspective, the first chimpanzee white matter atlas, constructed from in vivo chimpanzee diffusion-weighted scans. Comparative white matter atlases provide a useful tool for identifying neuroanatomical differences and similarities between humans and other primate species. Until now, comprehensive fascicular atlases have been created for humans (Homo sapiens), rhesus macaques (Macaca mulatta), and several other nonhuman primate species, but never in a nonhuman ape. Information on chimpanzee neuroanatomy is essential for understanding the anatomical specializations of white matter organization that are unique to the human lineage.


Assuntos
Pan troglodytes/anatomia & histologia , Substância Branca/anatomia & histologia , Anatomia Artística/métodos , Animais , Atlas como Assunto , Encéfalo/anatomia & histologia , Mapeamento Encefálico/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Imagem de Tensor de Difusão/métodos , Feminino , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Masculino
5.
PLoS One ; 15(12): e0242773, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33338084

RESUMO

Autism Spectrum Disorder (ASD) is a heterogeneous disorder that is often accompanied with many co-morbidities. Recent genetic studies have identified various pathways from hundreds of candidate risk genes with varying levels of association to ASD. However, it is unknown which pathways are specific to the core symptoms or which are shared by the co-morbidities. We hypothesised that critical ASD candidates should appear widely across different scoring systems, and that comorbidity pathways should be constituted by genes expressed in the relevant tissues. We analysed the Simons Foundation for Autism Research Initiative (SFARI) database and four independently published scoring systems and identified 292 overlapping genes. We examined their mRNA expression using the Genotype-Tissue Expression (GTEx) database and validated protein expression levels using the human protein atlas (HPA) dataset. This led to clustering of the overlapping ASD genes into 2 groups; one with 91 genes primarily expressed in the central nervous system (CNS geneset) and another with 201 genes expressed in both CNS and peripheral tissues (CNS+PT geneset). Bioinformatic analyses showed a high enrichment of CNS development and synaptic transmission in the CNS geneset, and an enrichment of synapse, chromatin remodelling, gene regulation and endocrine signalling in the CNS+PT geneset. Calcium signalling and the glutamatergic synapse were found to be highly interconnected among pathways in the combined geneset. Our analyses demonstrate that 2/3 of ASD genes are expressed beyond the brain, which may impact peripheral function and involve in ASD co-morbidities, and relevant pathways may be explored for the treatment of ASD co-morbidities.


Assuntos
Transtorno do Espectro Autista/genética , Sinalização do Cálcio/genética , Epilepsia/genética , Redes Reguladoras de Genes , Proteínas do Tecido Nervoso/genética , Transtornos da Personalidade/genética , Comportamento Autodestrutivo/genética , Adulto , Idoso , Atlas como Assunto , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/metabolismo , Transtorno do Espectro Autista/patologia , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/patologia , Cromatina/metabolismo , Cromatina/ultraestrutura , Comorbidade , Bases de Dados Genéticas , Conjuntos de Dados como Assunto , Epilepsia/diagnóstico , Epilepsia/metabolismo , Epilepsia/patologia , Feminino , Regulação da Expressão Gênica , Ontologia Genética , Humanos , Masculino , Pessoa de Meia-Idade , Anotação de Sequência Molecular , Proteínas do Tecido Nervoso/classificação , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Sistema Nervoso Periférico/metabolismo , Sistema Nervoso Periférico/patologia , Transtornos da Personalidade/diagnóstico , Transtornos da Personalidade/metabolismo , Transtornos da Personalidade/patologia , Comportamento Autodestrutivo/diagnóstico , Comportamento Autodestrutivo/metabolismo , Comportamento Autodestrutivo/patologia , Sinapses/metabolismo , Sinapses/patologia , Sinapses/ultraestrutura , Transmissão Sináptica , Transcrição Genética
6.
Science ; 369(6506): 988-992, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32732281

RESUMO

Cytoarchitecture is a basic principle of microstructural brain parcellation. We introduce Julich-Brain, a three-dimensional atlas containing cytoarchitectonic maps of cortical areas and subcortical nuclei. The atlas is probabilistic, which enables it to account for variations between individual brains. Building such an atlas was highly data- and labor-intensive and required the development of nested, interdependent workflows for detecting borders between brain areas, data processing, provenance tracking, and flexible execution of processing chains to handle large amounts of data at different spatial scales. Full cortical coverage was achieved by the inclusion of gap maps to complement cortical maps. The atlas is dynamic and will be adapted as mapping progresses; it is openly available to support neuroimaging studies as well as modeling and simulation; and it is interoperable, enabling connection to other atlases and resources.


Assuntos
Atlas como Assunto , Córtex Cerebral/ultraestrutura , Conjuntos de Dados como Assunto , Humanos , Imageamento Tridimensional , Imagem por Ressonância Magnética , Modelos Estatísticos
7.
Science ; 369(6501): 270-275, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32527927

RESUMO

Synapses connect neurons together to form the circuits of the brain, and their molecular composition controls innate and learned behavior. We analyzed the molecular and morphological diversity of 5 billion excitatory synapses at single-synapse resolution across the mouse brain from birth to old age. A continuum of changes alters synapse composition in all brain regions across the life span. Expansion in synapse diversity produces differentiation of brain regions until early adulthood, and compositional changes cause dedifferentiation in old age. The spatiotemporal synaptome architecture of the brain potentially accounts for life-span transitions in intellectual ability, memory, and susceptibility to behavioral disorders.


Assuntos
Encéfalo , Sinapses , Animais , Atlas como Assunto , Encéfalo/fisiologia , Encéfalo/ultraestrutura , Conjuntos de Dados como Assunto , Longevidade , Masculino , Camundongos , Neurônios/fisiologia , Sinapses/fisiologia , Sinaptossomos/fisiologia , Sinaptossomos/ultraestrutura
8.
Am J Pathol ; 190(7): 1565-1579, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32304697

RESUMO

Mitochondria regulate ATP production, metabolism, and cell death. Alterations in mitochondrial DNA (mtDNA) sequence and copy number are implicated in aging and organ dysfunction in diverse inherited and sporadic diseases. Because most measurements of mtDNA use homogenates of complex tissues, little is known about cell-type-specific mtDNA copy number heterogeneity in normal physiology, aging, and disease. Thus, the precise cell types whose loss of mitochondrial activity and altered mtDNA copy number that result in organ dysfunction in aging and disease have often not been clarified. Here, an in situ hybridization approach to generate a single-cell-resolution atlas of mtDNA content in mammalian tissues was validated. In hierarchically organized self-renewing tissues, higher levels of mtDNA were observed in stem/proliferative compartments compared with differentiated compartments. Striking zonal patterns of mtDNA levels in the liver reflected the known oxygen tension gradient. In the kidney, proximal and distal tubules had markedly higher mtDNA levels compared with cells within glomeruli and collecting duct epithelial cells. In mice, decreased mtDNA levels were visualized in renal tubules as a function of aging, which was prevented by calorie restriction. This study provides a novel approach for quantifying species- and cell-type-specific mtDNA copy number and dynamics in any normal or diseased tissue that can be used for monitoring the effects of interventions in animal and human studies.


Assuntos
Proliferação de Células , DNA Mitocondrial/análise , Células-Tronco , Envelhecimento/fisiologia , Animais , Atlas como Assunto , Variações do Número de Cópias de DNA , Feminino , Humanos , Hibridização In Situ/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
9.
Cell ; 181(2): 236-249, 2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-32302568

RESUMO

Crucial transitions in cancer-including tumor initiation, local expansion, metastasis, and therapeutic resistance-involve complex interactions between cells within the dynamic tumor ecosystem. Transformative single-cell genomics technologies and spatial multiplex in situ methods now provide an opportunity to interrogate this complexity at unprecedented resolution. The Human Tumor Atlas Network (HTAN), part of the National Cancer Institute (NCI) Cancer Moonshot Initiative, will establish a clinical, experimental, computational, and organizational framework to generate informative and accessible three-dimensional atlases of cancer transitions for a diverse set of tumor types. This effort complements both ongoing efforts to map healthy organs and previous large-scale cancer genomics approaches focused on bulk sequencing at a single point in time. Generating single-cell, multiparametric, longitudinal atlases and integrating them with clinical outcomes should help identify novel predictive biomarkers and features as well as therapeutically relevant cell types, cell states, and cellular interactions across transitions. The resulting tumor atlases should have a profound impact on our understanding of cancer biology and have the potential to improve cancer detection, prevention, and therapeutic discovery for better precision-medicine treatments of cancer patients and those at risk for cancer.


Assuntos
Transformação Celular Neoplásica/metabolismo , Neoplasias/metabolismo , Microambiente Tumoral/fisiologia , Atlas como Assunto , Transformação Celular Neoplásica/patologia , Genômica/métodos , Humanos , Medicina de Precisão/métodos , Análise de Célula Única/métodos
10.
Nat Commun ; 11(1): 1133, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111833

RESUMO

Understanding the principles of neuronal connectivity requires tools for efficient quantification and visualization of large datasets. The primate cortex is particularly challenging due to its complex mosaic of areas, which in many cases lack clear boundaries. Here, we introduce a resource that allows exploration of results of 143 retrograde tracer injections in the marmoset neocortex. Data obtained in different animals are registered to a common stereotaxic space using an algorithm guided by expert delineation of histological borders, allowing accurate assignment of connections to areas despite interindividual variability. The resource incorporates tools for analyses relative to cytoarchitectural areas, including statistical properties such as the fraction of labeled neurons and the percentage of supragranular neurons. It also provides purely spatial (parcellation-free) data, based on the stereotaxic coordinates of 2 million labeled neurons. This resource helps bridge the gap between high-density cellular connectivity studies in rodents and imaging-based analyses of human brains.


Assuntos
Atlas como Assunto , Encéfalo/anatomia & histologia , Callithrix/anatomia & histologia , Animais , Encéfalo/metabolismo , Encéfalo/fisiologia , Mapeamento Encefálico , Callithrix/fisiologia , Imageamento Tridimensional , Neocórtex/citologia , Neocórtex/metabolismo , Neocórtex/fisiologia , Vias Neurais , Marcadores do Trato Nervoso/administração & dosagem , Marcadores do Trato Nervoso/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Neurônios/fisiologia
11.
Science ; 367(6482)2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-32139519

RESUMO

The brain, with its diverse physiology and intricate cellular organization, is the most complex organ of the mammalian body. To expand our basic understanding of the neurobiology of the brain and its diseases, we performed a comprehensive molecular dissection of 10 major brain regions and multiple subregions using a variety of transcriptomics methods and antibody-based mapping. This analysis was carried out in the human, pig, and mouse brain to allow the identification of regional expression profiles, as well as to study similarities and differences in expression levels between the three species. The resulting data have been made available in an open-access Brain Atlas resource, part of the Human Protein Atlas, to allow exploration and comparison of the expression of individual protein-coding genes in various parts of the mammalian brain.


Assuntos
Atlas como Assunto , Encéfalo/fisiologia , Regulação da Expressão Gênica , Proteínas do Tecido Nervoso/genética , Transcriptoma , Animais , Conjuntos de Dados como Assunto , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Especificidade de Órgãos/genética , Especificidade da Espécie , Suínos
12.
Cancer Res ; 80(10): 2067-2071, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32193291

RESUMO

Long noncoding RNAs (lncRNA) play important roles in maintaining morphology and function of tissues, and their regulatory effectiveness is closely associated with spatial expression. To provide a comprehensive spatial atlas of expression for lncRNA, we propose LncSpA (http://bio-bigdata.hrbmu.edu.cn/LncSpA) to explore tissue-elevated (TE) lncRNA across human normal and adult and pediatric cancer tissues. In total, 71,131 and 12,007 TE lncRNAs and 634 clinical-related TE lncRNAs were identified across 38 normal and 33 adult cancer tissues. Moreover, 4,688 TE and 413 clinical-related lncRNAs were identified in pediatric cancer. By quick searching or query options, users can obtain eight major types of detailed information for lncRNA via various visualization techniques, including qualitative and quantitative spatial expression in different resources, coexpressed mRNAs, predicted function, known disease association, and the potential to serve as diagnostic or prognostic markers. LncSpA will be a valuable resource to understand lncRNA functions across tissues and cancers, leading to enhanced therapeutic strategies in precision oncology. SIGNIFICANCE: LncSpA is a new interactive resource that provides the spatial expression pattern of lncRNA across thousands of normal and cancer samples representing major tissue types.


Assuntos
Atlas como Assunto , Bases de Dados Genéticas , RNA Longo não Codificante/análise , Transcriptoma , Perfilação da Expressão Gênica/métodos , Humanos , Internet , Neoplasias/genética
13.
Development ; 147(6)2020 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-32094115

RESUMO

Segmentation of the vertebrate hindbrain leads to the formation of rhombomeres, each with a distinct anteroposterior identity. Specialised boundary cells form at segment borders that act as a source or regulator of neuronal differentiation. In zebrafish, there is spatial patterning of neurogenesis in which non-neurogenic zones form at boundaries and segment centres, in part mediated by Fgf20 signalling. To further understand the control of neurogenesis, we have carried out single cell RNA sequencing of the zebrafish hindbrain at three different stages of patterning. Analyses of the data reveal known and novel markers of distinct hindbrain segments, of cell types along the dorsoventral axis, and of the transition of progenitors to neuronal differentiation. We find major shifts in the transcriptome of progenitors and of differentiating cells between the different stages analysed. Supervised clustering with markers of boundary cells and segment centres, together with RNA-seq analysis of Fgf-regulated genes, has revealed new candidate regulators of cell differentiation in the hindbrain. These data provide a valuable resource for functional investigations of the patterning of neurogenesis and the transition of progenitors to neuronal differentiation.


Assuntos
Padronização Corporal/genética , Rombencéfalo/embriologia , Rombencéfalo/metabolismo , Transcriptoma/fisiologia , Peixe-Zebra , Animais , Animais Geneticamente Modificados , Atlas como Assunto , Diferenciação Celular/genética , Embrião não Mamífero , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Neurogênese/genética , Neurônios/citologia , Neurônios/fisiologia , Análise de Célula Única/métodos , Distribuição Tecidual , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
14.
Science ; 367(6480)2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-32079746

RESUMO

The thymus provides a nurturing environment for the differentiation and selection of T cells, a process orchestrated by their interaction with multiple thymic cell types. We used single-cell RNA sequencing to create a cell census of the human thymus across the life span and to reconstruct T cell differentiation trajectories and T cell receptor (TCR) recombination kinetics. Using this approach, we identified and located in situ CD8αα+ T cell populations, thymic fibroblast subtypes, and activated dendritic cell states. In addition, we reveal a bias in TCR recombination and selection, which is attributed to genomic position and the kinetics of lineage commitment. Taken together, our data provide a comprehensive atlas of the human thymus across the life span with new insights into human T cell development.


Assuntos
Atlas como Assunto , Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular , Timo/crescimento & desenvolvimento , Timo/imunologia , Linfócitos T CD8-Positivos/citologia , Células Dendríticas/citologia , Células Dendríticas/imunologia , Fibroblastos/citologia , Fibroblastos/imunologia , Humanos , RNA-Seq/métodos , Receptores de Antígenos de Linfócitos T/metabolismo , Análise de Célula Única/métodos , Timo/citologia
15.
Sci Rep ; 10(1): 2757, 2020 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066851

RESUMO

Homologous recombination repair (HRR) pathway deficiency (HRD) is involved in the tumorigenesis and progression of high-grade serous ovarian carcinoma (HGSOC) as well as in the sensitivity to platinum chemotherapy drugs. In this study, we obtained data from The Cancer Genome Atlas (TCGA) on HGSOC and identified scores for the loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions, and calculated the HRD score. We then investigated the relationships among the score, genetic/epigenetic alterations in HRR-related genes, and the clinical data. We found that BRCA1/2 mutations were enriched in the group with HRD scores ≥63. Compared with the groups with scores ≤62, this group had a good prognosis; we thus considered HRD scores ≥63 to be the best cutoff point for identifying HRD cases in HGSOC. Classification of HGSOC cases by the HRD status revealed a better prognosis for HRD cases caused by genetic alterations (genetic HRD) than those caused by epigenetic changes and those caused by undetermined reasons (p = 0.0002). Among cases without macroscopic residual tumors after primary debulking surgery, 11 of 12 genetic HRD cases survived after the median observation period of 6.6 years, showing remarkably high survival rates (p = 0.0059). In conclusion, HGSOC can be classified into subtypes with different prognoses according to HRD status. This classification could be useful for personalized HGSOC treatment.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Cistadenocarcinoma Seroso/diagnóstico , DNA de Neoplasias/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas/diagnóstico , Reparo de DNA por Recombinação , Desequilíbrio Alélico , Atlas como Assunto , Proteína BRCA1/metabolismo , Proteína BRCA2/metabolismo , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/cirurgia , DNA de Neoplasias/metabolismo , Epigênese Genética , Feminino , Humanos , Perda de Heterozigosidade , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Medicina de Precisão , Prognóstico , Análise de Sobrevida , Terminologia como Assunto
16.
Nat Neurosci ; 23(3): 456-467, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32066983

RESUMO

Mammalian circadian behaviors are orchestrated by the suprachiasmatic nucleus (SCN) in the ventral hypothalamus, but the number of SCN cell types and their functional roles remain unclear. We have used single-cell RNA-sequencing to identify the basic cell types in the mouse SCN and to characterize their circadian and light-induced gene expression patterns. We identified eight major cell types, with each type displaying a specific pattern of circadian gene expression. Five SCN neuronal subtypes, each with specific combinations of markers, differ in their spatial distribution, circadian rhythmicity and light responsiveness. Through a complete three-dimensional reconstruction of the mouse SCN at single-cell resolution, we obtained a standardized SCN atlas containing the spatial distribution of these subtypes and gene expression. Furthermore, we observed heterogeneous circadian gene expression between SCN neuron subtypes. Such a spatiotemporal pattern of gene regulation within the SCN may have an important function in the circadian pacemaker.


Assuntos
Expressão Gênica/fisiologia , Neurônios/fisiologia , Análise de Célula Única , Núcleo Supraquiasmático/fisiologia , Animais , Atlas como Assunto , Ritmo Circadiano/fisiologia , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/genética , Expressão Gênica/efeitos da radiação , Regulação da Expressão Gênica/fisiologia , Genômica , Luz , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/classificação , Estimulação Luminosa , Núcleo Supraquiasmático/anatomia & histologia , Núcleo Supraquiasmático/citologia
17.
Cell ; 180(3): 585-600.e19, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32004457

RESUMO

Molecular mechanisms of ovarian aging and female age-related fertility decline remain unclear. We surveyed the single-cell transcriptomic landscape of ovaries from young and aged non-human primates (NHPs) and identified seven ovarian cell types with distinct gene-expression signatures, including oocyte and six types of ovarian somatic cells. In-depth dissection of gene-expression dynamics of oocytes revealed four subtypes at sequential and stepwise developmental stages. Further analysis of cell-type-specific aging-associated transcriptional changes uncovered the disturbance of antioxidant signaling specific to early-stage oocytes and granulosa cells, indicative of oxidative damage as a crucial factor in ovarian functional decline with age. Additionally, inactivated antioxidative pathways, increased reactive oxygen species, and apoptosis were observed in granulosa cells from aged women. This study provides a comprehensive understanding of the cell-type-specific mechanisms underlying primate ovarian aging at single-cell resolution, revealing new diagnostic biomarkers and potential therapeutic targets for age-related human ovarian disorders.


Assuntos
Envelhecimento/genética , Ovário/fisiologia , Análise de Célula Única/métodos , Transcriptoma , Idoso , Animais , Antioxidantes/metabolismo , Apoptose/fisiologia , Atlas como Assunto , Biomarcadores , Linhagem Celular Tumoral , Feminino , Células da Granulosa/metabolismo , Humanos , Macaca fascicularis , Oócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/fisiologia
18.
Brain Struct Funct ; 225(2): 683-703, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32009190

RESUMO

The phylogenetic position of crocodilians in relation to birds and mammals makes them an interesting animal model for investigating the evolution of the nervous system in amniote vertebrates. A few neuroanatomical atlases are available for reptiles, but with a growing interest in these animals within the comparative neurosciences, a need for these anatomical reference templates is becoming apparent. With the advent of MRI being used more frequently in comparative neuroscience, the aim of this study was to create a three-dimensional MRI-based atlas of the Nile crocodile (Crocodylus niloticus) brain to provide a common reference template for the interpretation of the crocodilian, and more broadly reptilian, brain. Ex vivo MRI acquisitions in combination with histological data were used to delineate crocodilian brain areas at telencephalic, diencephalic, mesencephalic, and rhombencephalic levels. A total of 50 anatomical structures were successfully identified and outlined to create a 3-D model of the Nile crocodile brain. The majority of structures were more readily discerned within the forebrain of the crocodile with the methods used to produce this atlas. The anatomy outlined herein corresponds with both classical and recent crocodilian anatomical analyses, barring a few areas of contention predominantly related to a lack of functional data and conflicting nomenclature.


Assuntos
Jacarés e Crocodilos/anatomia & histologia , Anatomia Artística , Atlas como Assunto , Prosencéfalo/anatomia & histologia , Animais , Imagem por Ressonância Magnética , Filogenia , Prosencéfalo/diagnóstico por imagem
19.
Neuroinformatics ; 18(2): 319-331, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31898145

RESUMO

Segmentation of medical images using multiple atlases has recently gained immense attention due to their augmented robustness against variabilities across different subjects. These atlas-based methods typically comprise of three steps: atlas selection, image registration, and finally label fusion. Image registration is one of the core steps in this process, accuracy of which directly affects the final labeling performance. However, due to inter-subject anatomical variations, registration errors are inevitable. The aim of this paper is to develop a deep learning-based confidence estimation method to alleviate the potential effects of registration errors. We first propose a fully convolutional network (FCN) with residual connections to learn the relationship between the image patch pair (i.e., patches from the target subject and the atlas) and the related label confidence patch. With the obtained label confidence patch, we can identify the potential errors in the warped atlas labels and correct them. Then, we use two label fusion methods to fuse the corrected atlas labels. The proposed methods are validated on a publicly available dataset for hippocampus segmentation. Experimental results demonstrate that our proposed methods outperform the state-of-the-art segmentation methods.


Assuntos
Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos , Neuroimagem/métodos , Atlas como Assunto , Hipocampo/anatomia & histologia , Hipocampo/fisiologia , Humanos , Imagem por Ressonância Magnética/métodos
20.
Med Hist ; 64(1): 116-141, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31933505

RESUMO

In early twentieth-century France, syphilis and its controversial status as a hereditary disease reigned as a chief concern for physicians and public health officials. As syphilis primarily presented visually on the surface of the skin, its study fell within the realms of both dermatologists and venereologists, who relied heavily on visual evidence in their detection, diagnosis, and treatment of the disease. Thus, in educational textbooks, atlases, and medical models, accurately reproducing the visible signposts of syphilis - the colour, texture, and patterns of primary chancres or secondary rashes - was of preeminent importance. Photography, with its potential claims to mechanical objectivity, would seem to provide the logical tool for such representations. Yet photography's relationship to syphilographie warrants further unpacking. Despite the rise of a desire for mechanical objectivity charted in the late nineteenth century, artist-produced, three-dimensional, wax-cast moulages coexisted with photographs as significant educational tools for dermatologists; at times, these models were further mediated through photographic reproduction in texts. Additionally, the rise of phototherapy complicated this relationship by fostering the clinical equation of the light-sensitive photographic plate with the patient's skin, which became the photographic record of disease and successful treatment. This paper explores these complexities to delineate a more nuanced understanding of objectivity vis-à-vis photography and syphilis. Rather than a desire to produce an unbiased image, fin-de-siècle dermatologists marshalled the photographic to exploit the verbal and visual rhetoric of objectivity, authority, and persuasion inextricably linked to culturally constructed understandings of the photograph. This rhetoric was often couched in the Peircean concept of indexicality, which physicians formulated through the language of witness, testimony, and direct connection.


Assuntos
Anatomia Artística/história , Ilustração Médica/história , Modelos Anatômicos , Fotografação/história , Sífilis/história , Atlas como Assunto/história , Distinções e Prêmios , Dermatologia/educação , Dermatologia/história , França , Historiografia , História do Século XIX , História do Século XX , Humanos , Sífilis/patologia , Sífilis Congênita/história , Venereologia/educação , Venereologia/história
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