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2.
Nat Neurosci ; 24(4): 572-583, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33589834

RESUMO

The spinal cord is a fascinating structure that is responsible for coordinating movement in vertebrates. Spinal motor neurons control muscle activity by transmitting signals from the spinal cord to diverse peripheral targets. In this study, we profiled 43,890 single-nucleus transcriptomes from the adult mouse spinal cord using fluorescence-activated nuclei sorting to enrich for motor neuron nuclei. We identified 16 sympathetic motor neuron clusters, which are distinguishable by spatial localization and expression of neuromodulatory signaling genes. We found surprising skeletal motor neuron heterogeneity in the adult spinal cord, including transcriptional differences that correlate with electrophysiologically and spatially distinct motor pools. We also provide evidence for a novel transcriptional subpopulation of skeletal motor neuron (γ*). Collectively, these data provide a single-cell transcriptional atlas ( http://spinalcordatlas.org ) for investigating the organizing molecular logic of adult motor neuron diversity, as well as the cellular and molecular basis of motor neuron function in health and disease.


Assuntos
Neurônios Motores/citologia , Músculo Esquelético/inervação , Medula Espinal/citologia , Vísceras/inervação , Animais , Sistema Nervoso Autônomo , Camundongos , Análise de Célula Única , Transcriptoma
3.
Neuron ; 108(5): 822-842, 2020 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-32931756

RESUMO

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder caused by the loss of motor neurons from the brain and spinal cord. The ALS community has made remarkable strides over three decades by identifying novel familial mutations, generating animal models, elucidating molecular mechanisms, and ultimately developing promising new therapeutic approaches. Some of these approaches reduce the expression of mutant genes and are in human clinical trials, highlighting the need to carefully consider the normal functions of these genes and potential contribution of gene loss-of-function to ALS. Here, we highlight known loss-of-function mechanisms underlying ALS, potential consequences of lowering levels of gene products, and the need to consider both gain and loss of function to develop safe and effective therapeutic strategies.


Assuntos
Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/terapia , Mutação com Ganho de Função/genética , Terapia Genética/tendências , Mutação com Perda de Função/genética , Animais , Proteína C9orf72/genética , Previsões , Humanos , Superóxido Dismutase-1/genética
4.
Cell Res ; 34(3): 181-182, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38177241
6.
Science ; 359(6382): 1403-1407, 2018 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-29567713

RESUMO

Lymph node metastases in cancer patients are associated with tumor aggressiveness, poorer prognoses, and the recommendation for systemic therapy. Whether cancer cells in lymph nodes can seed distant metastases has been a subject of considerable debate. We studied mice implanted with cancer cells (mammary carcinoma, squamous cell carcinoma, or melanoma) expressing the photoconvertible protein Dendra2. This technology allowed us to selectively photoconvert metastatic cells in the lymph node and trace their fate. We found that a fraction of these cells invaded lymph node blood vessels, entered the blood circulation, and colonized the lung. Thus, in mouse models, lymph node metastases can be a source of cancer cells for distant metastases. Whether this mode of dissemination occurs in cancer patients remains to be determined.


Assuntos
Vasos Sanguíneos/patologia , Linfonodos/patologia , Metástase Linfática/patologia , Inoculação de Neoplasia , Animais , Carcinoma de Células Escamosas , Linhagem Celular Tumoral , Movimento Celular , Rastreamento de Células/métodos , Citosol/química , Feminino , Proteínas Luminescentes/análise , Pulmão/patologia , Melanoma Experimental , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Células Neoplásicas Circulantes
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