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1.
Nature ; 535(7612): 367-75, 2016 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-27409810

RESUMO

The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high-resolution transcriptional atlas of rhesus monkey (Macaca mulatta) brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical division of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons. Cortical layers and areas acquire adult-like molecular profiles surprisingly late in postnatal development. Disparate cell populations exhibit distinct developmental timing of gene expression, but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, autism spectrum disorder, intellectual disability, and schizophrenia show disease-specific spatiotemporal enrichment within developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, although approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny compared to monkey.


Assuntos
Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Macaca mulatta/genética , Transcriptoma , Envelhecimento/genética , Animais , Transtorno do Espectro Autista/genética , Encéfalo/citologia , Encéfalo/embriologia , Adesão Celular , Sequência Conservada , Feminino , Humanos , Deficiência Intelectual/genética , Masculino , Microcefalia/genética , Neocórtex/embriologia , Neocórtex/crescimento & desenvolvimento , Neocórtex/metabolismo , Transtornos do Neurodesenvolvimento/genética , Neurogênese/genética , Fatores de Risco , Esquizofrenia/genética , Análise Espaço-Temporal , Especificidade da Espécie , Transcrição Gênica/genética
2.
Nature ; 508(7495): 199-206, 2014 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-24695229

RESUMO

The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development.


Assuntos
Encéfalo/metabolismo , Feto/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Transcriptoma , Anatomia Artística , Animais , Atlas como Assunto , Encéfalo/embriologia , Sequência Conservada/genética , Feto/citologia , Feto/embriologia , Redes Reguladoras de Genes/genética , Humanos , Camundongos , Neocórtex/embriologia , Neocórtex/metabolismo , Especificidade da Espécie
3.
Nature ; 489(7416): 391-399, 2012 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-22996553

RESUMO

Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ∼900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography-the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function.


Assuntos
Anatomia Artística , Atlas como Assunto , Encéfalo/anatomia & histologia , Encéfalo/metabolismo , Perfilação da Expressão Gênica , Transcriptoma/genética , Adulto , Animais , Encéfalo/citologia , Calbindinas , Bases de Dados Genéticas , Dopamina/metabolismo , Saúde , Hipocampo/citologia , Hipocampo/metabolismo , Humanos , Hibridização In Situ , Internet , Macaca mulatta/anatomia & histologia , Macaca mulatta/genética , Masculino , Camundongos , Neocórtex/anatomia & histologia , Neocórtex/citologia , Neocórtex/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Densidade Pós-Sináptica/genética , RNA Mensageiro/análise , RNA Mensageiro/genética , Proteína G de Ligação ao Cálcio S100/genética , Especificidade da Espécie
4.
Development ; 140(22): 4633-44, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24154525

RESUMO

The neurogenic potential of the subgranular zone (SGZ) of the hippocampal dentate gyrus is likely to be regulated by molecular cues arising from its complex heterogeneous cellular environment. Through transcriptome analysis using laser microdissection coupled with DNA microarrays, in combination with analysis of genome-wide in situ hybridization data, we identified 363 genes selectively enriched in adult mouse SGZ. These genes reflect expression in the different constituent cell types, including progenitor and dividing cells, immature granule cells, astrocytes, oligodendrocytes and GABAergic interneurons. Similar transcriptional profiling in the rhesus monkey dentate gyrus across postnatal development identified a highly overlapping set of SGZ-enriched genes, which can be divided based on temporal profiles to reflect maturation of glia versus granule neurons. Furthermore, we identified a neurogenesis-related gene network with decreasing postnatal expression that is highly correlated with the declining number of proliferating cells in dentate gyrus over postnatal development. Many of the genes in this network showed similar postnatal downregulation in mouse, suggesting a conservation of molecular mechanisms underlying developmental and adult neurogenesis in rodents and primates. Conditional deletion of Sox4 and Sox11, encoding two neurogenesis-related transcription factors central in this network, produces a mouse with no hippocampus, confirming the crucial role for these genes in regulating hippocampal neurogenesis.


Assuntos
Perfilação da Expressão Gênica , Hipocampo/metabolismo , Macaca mulatta/genética , Neurogênese/genética , Animais , Animais Recém-Nascidos , Biomarcadores/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Genoma/genética , Hipocampo/citologia , Interneurônios/citologia , Interneurônios/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Família Multigênica , Oligodendroglia/citologia , Oligodendroglia/metabolismo , Fatores de Transcrição SOXC/genética , Fatores de Transcrição SOXC/metabolismo , Análise Espaço-Temporal , Transcrição Gênica
5.
Mol Cell Proteomics ; 10(9): M110.006908, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21610103

RESUMO

The mitochondrial respiratory chain is comprised of four different protein complexes (I-IV), which are responsible for electron transport and generation of proton gradient in the mitochondrial intermembrane space. This proton gradient is then used by F0F1-ATP synthase (complex V) to produce ATP by oxidative phosphorylation. In this study, the respiratory complexes I, II, and III were affinity purified from Trypanosoma brucei procyclic form cells and their composition was determined by mass spectrometry. The results along with those that we previously reported for complexes IV and V showed that the respiratome of Trypanosoma is divergent because many of its proteins are unique to this group of organisms. The studies also identified two mitochondrial subunit proteins of respiratory complex IV that are encoded by edited RNAs. Proteomics data from analyses of complexes purified using numerous tagged component proteins in each of the five complexes were used to generate the first predicted protein-protein interaction network of the Trypanosoma brucei respiratory chain. These results provide the first comprehensive insight into the unique composition of the respiratory complexes in Trypanosoma brucei, an early diverged eukaryotic pathogen.


Assuntos
Transporte de Elétrons/genética , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Mapeamento de Interação de Proteínas/métodos , Proteoma/metabolismo , Proteômica/métodos , Proteínas de Protozoários/metabolismo , Trypanosoma brucei brucei , Animais , Sequência de Bases , Cromatografia de Afinidade , Complexo I de Transporte de Elétrons/química , Complexo I de Transporte de Elétrons/metabolismo , Complexo II de Transporte de Elétrons/química , Complexo II de Transporte de Elétrons/metabolismo , Complexo III da Cadeia de Transporte de Elétrons/química , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/química , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Humanos , Espectrometria de Massas , Mitocôndrias/genética , Proteínas Mitocondriais/genética , Dados de Sequência Molecular , Mapas de Interação de Proteínas/genética , Proteoma/química , Proteoma/genética , Proteínas de Protozoários/genética , Edição de RNA , Trypanosoma brucei brucei/química , Trypanosoma brucei brucei/genética , Trypanosoma brucei brucei/metabolismo , Tripanossomíase Africana/parasitologia
6.
J Comp Neurol ; 530(1): 6-503, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34525221

RESUMO

Increasing interest in studies of prenatal human brain development, particularly using new single-cell genomics and anatomical technologies to create cell atlases, creates a strong need for accurate and detailed anatomical reference atlases. In this study, we present two cellular-resolution digital anatomical atlases for prenatal human brain at postconceptional weeks (PCW) 15 and 21. Both atlases were annotated on sequential Nissl-stained sections covering brain-wide structures on the basis of combined analysis of cytoarchitecture, acetylcholinesterase staining, and an extensive marker gene expression dataset. This high information content dataset allowed reliable and accurate demarcation of developing cortical and subcortical structures and their subdivisions. Furthermore, using the anatomical atlases as a guide, spatial expression of 37 and 5 genes from the brains, respectively, at PCW 15 and 21 was annotated, illustrating reliable marker genes for many developing brain structures. Finally, the present study uncovered several novel developmental features, such as the lack of an outer subventricular zone in the hippocampal formation and entorhinal cortex, and the apparent extension of both cortical (excitatory) and subcortical (inhibitory) progenitors into the prenatal olfactory bulb. These comprehensive atlases provide useful tools for visualization, segmentation, targeting, imaging, and interpretation of brain structures of prenatal human brain, and for guiding and interpreting the next generation of cell census and connectome studies.


Assuntos
Atlas como Assunto , Encéfalo/crescimento & desenvolvimento , Córtex Entorrinal/crescimento & desenvolvimento , Hipocampo/crescimento & desenvolvimento , Animais , Feminino , Humanos , Gravidez
7.
PLoS Pathog ; 5(5): e1000436, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19436713

RESUMO

The mitochondrial F(0)F(1) ATP synthase is an essential multi-subunit protein complex in the vast majority of eukaryotes but little is known about its composition and role in Trypanosoma brucei, an early diverged eukaryotic pathogen. We purified the F(0)F(1) ATP synthase by a combination of affinity purification, immunoprecipitation and blue-native gel electrophoresis and characterized its composition and function. We identified 22 proteins of which five are related to F(1) subunits, three to F(0) subunits, and 14 which have no obvious homology to proteins outside the kinetoplastids. RNAi silencing of expression of the F(1) alpha subunit or either of the two novel proteins showed that they are each essential for the viability of procyclic (insect stage) cells and are important for the structural integrity of the F(0)F(1)-ATP synthase complex. We also observed a dramatic decrease in ATP production by oxidative phosphorylation after silencing expression of each of these proteins while substrate phosphorylation was not severely affected. Our procyclic T. brucei cells were sensitive to the ATP synthase inhibitor oligomycin even in the presence of glucose contrary to earlier reports. Hence, the two novel proteins appear essential for the structural organization of the functional complex and regulation of mitochondrial energy generation in these organisms is more complicated than previously thought.


Assuntos
ATPases Mitocondriais Próton-Translocadoras/fisiologia , Trypanosoma brucei brucei/enzimologia , Trifosfato de Adenosina/metabolismo , Animais , Inibidores Enzimáticos/farmacologia , Técnicas de Silenciamento de Genes , Glucose/metabolismo , Imunoprecipitação , ATPases Mitocondriais Próton-Translocadoras/antagonistas & inibidores , ATPases Mitocondriais Próton-Translocadoras/química , ATPases Mitocondriais Próton-Translocadoras/genética , Oligomicinas/farmacologia , Subunidades Proteicas/fisiologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/fisiologia , Interferência de RNA , Azida Sódica/farmacologia , Trypanosoma brucei brucei/efeitos dos fármacos , Trypanosoma brucei brucei/crescimento & desenvolvimento
8.
Elife ; 102021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34387544

RESUMO

The Patch-seq approach is a powerful variation of the patch-clamp technique that allows for the combined electrophysiological, morphological, and transcriptomic characterization of individual neurons. To generate Patch-seq datasets at scale, we identified and refined key factors that contribute to the efficient collection of high-quality data. We developed patch-clamp electrophysiology software with analysis functions specifically designed to automate acquisition with online quality control. We recognized the importance of extracting the nucleus for transcriptomic success and maximizing membrane integrity during nucleus extraction for morphology success. The protocol is generalizable to different species and brain regions, as demonstrated by capturing multimodal data from human and macaque brain slices. The protocol, analysis and acquisition software are compiled at https://githubcom/AllenInstitute/patchseqtools. This resource can be used by individual labs to generate data across diverse mammalian species and that is compatible with large publicly available Patch-seq datasets.


Assuntos
Fenômenos Eletrofisiológicos , Análise de Célula Única/métodos , Transcriptoma , Animais , Encéfalo , Humanos , Macaca mulatta , Camundongos , Neurônios/citologia , Neurônios/fisiologia , Técnicas de Patch-Clamp , Software
9.
Mol Cell Proteomics ; 7(3): 534-45, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18073385

RESUMO

African trypanosomes, early diverged eukaryotes and the agents of sleeping sickness, have several basic cellular processes that are remarkably divergent from those in their mammalian hosts. They have large mitochondria and switch between oxidative phosphorylation and glycolysis as the major pathways for energy generation during their life cycle. We report here the identification and characterization of several multiprotein mitochondrial complexes from procyclic form Trypanosoma brucei. These were identified and purified using a panel of monoclonal antibodies that were generated against a submitochondrial protein fraction and using tandem affinity purification (TAP) tag affinity chromatography and localized within the cells by immunofluorescence. Protein composition analyses by mass spectrometry revealed substantial divergence of oxidoreductase complex from that of other organisms and identified a novel complex that may have a function associated with nucleic acids. The relationship to divergent physiological processes in these pathogens is discussed.


Assuntos
Mitocôndrias/enzimologia , Proteínas Mitocondriais/metabolismo , Complexos Multiproteicos/metabolismo , Oxirredutases/metabolismo , Trypanosoma brucei brucei/enzimologia , Animais , Anticorpos Monoclonais/metabolismo , Anticorpos Antiprotozoários/metabolismo , Western Blotting , Linhagem Celular , Fracionamento Químico , Imunofluorescência , Imunoprecipitação , Proteínas Mitocondriais/química , Complexos Multiproteicos/isolamento & purificação , Oxirredutases/química , Transporte Proteico , Proteínas de Protozoários/química , Proteínas de Protozoários/metabolismo , Análise de Sequência de Proteína , Frações Subcelulares/metabolismo , Trypanosoma brucei brucei/citologia
10.
Mol Cell Proteomics ; 7(7): 1286-96, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18364347

RESUMO

Although eukaryotic mitochondrial (mt) ribosomes evolved from a putative prokaryotic ancestor their compositions vary considerably among organisms. We determined the protein composition of tandem affinity-purified Trypanosoma brucei mt ribosomes by mass spectrometry and identified 133 proteins of which 77 were associated with the large subunit and 56 were associated with the small subunit. Comparisons with bacterial and mammalian mt ribosomal proteins identified T. brucei mt homologs of L2-4, L7/12, L9, L11, L13-17, L20-24, L27-30, L33, L38, L43, L46, L47, L49, L52, S5, S6, S8, S9, S11, S15-18, S29, and S34, although the degree of conservation varied widely. Sequence characteristics of some of the component proteins indicated apparent functions in rRNA modification and processing, protein assembly, and mitochondrial metabolism implying possible additional roles for these proteins. Nevertheless most of the identified proteins have no homology outside Kinetoplastida implying very low conservation and/or a divergent function in kinetoplastid mitochondria.


Assuntos
Mitocôndrias/química , Ribossomos/química , Trypanosoma brucei brucei/química , Algoritmos , Animais , Animais Geneticamente Modificados , Células Cultivadas , Cromatografia de Afinidade , Espectrometria de Massas , Mitocôndrias/metabolismo , Proteínas Ribossômicas/química , Subunidades Ribossômicas/química , Ribossomos/metabolismo , Coloração e Rotulagem/métodos , Trypanosoma brucei brucei/genética , Trypanosoma brucei brucei/metabolismo
11.
Proteomics ; 9(2): 434-50, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19105172

RESUMO

The composition of the large, single, mitochondrion (mt) of Trypanosoma brucei was characterized by MS (2-D LC-MS/MS and gel-LC-MS/MS) analyses. A total of 2897 proteins representing a substantial proportion of procyclic form cellular proteome were identified, which confirmed the validity of the vast majority of gene predictions. The data also showed that the genes annotated as hypothetical (species specific) were overpredicted and that virtually all genes annotated as hypothetical, unlikely are not expressed. By comparing the MS data with genome sequence, 40 genes were identified that were not previously predicted. The data are placed in a publicly available web-based database (www.TrypsProteome.org). The total mitochondrial proteome is estimated at 1008 proteins, with 401, 196, and 283 assigned to the mt with high, moderate, and lower confidence, respectively. The remaining mitochondrial proteins were estimated by statistical methods although individual assignments could not be made. The identified proteins have predicted roles in macromolecular, metabolic, energy generating, and transport processes providing a comprehensive profile of the protein content and function of the T. brucei mt.


Assuntos
Proteínas Mitocondriais/análise , Proteínas de Protozoários/análise , Trypanosoma brucei brucei/metabolismo , Animais , Fracionamento Celular , Bases de Dados de Proteínas , Internet , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Modelos Biológicos , Proteômica , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Reprodutibilidade dos Testes , Análise de Sequência de Proteína , Espectrometria de Massas em Tandem , Trypanosoma brucei brucei/genética
12.
Eukaryot Cell ; 7(11): 1994-2003, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18776036

RESUMO

A mitochondrial inner membrane protein, designated MIX, seems to be essential for cell viability. The deletion of both alleles was not possible, and the deletion of a single allele led to a loss of virulence and aberrant mitochondrial segregation and cell division in Leishmania major. However, the mechanism by which MIX exerts its effect has not been determined. We show here that MIX is also expressed in the mitochondrion of Trypanosoma brucei, and using RNA interference, we found that its loss leads to a phenotype that is similar to that described for Leishmania. The loss of MIX also had a major effect on cytochrome c oxidase activity, on the mitochondrial membrane potential, and on the production of mitochondrial ATP by oxidative phosphorylation. Using a tandem affinity purification tag, we found that MIX is associated with a multiprotein complex that contains subunits of the mitochondrial cytochrome c oxidase complex (respiratory complex IV), the composition of which was characterized in detail. The specific function of MIX is unknown, but it appears to be important for the function of complex IV and for mitochondrial segregation and cell division in T. brucei.


Assuntos
Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas de Protozoários/metabolismo , Trypanosoma brucei brucei/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Divisão Celular , Complexo IV da Cadeia de Transporte de Elétrons/genética , Expressão Gênica , Potencial da Membrana Mitocondrial , Proteínas Mitocondriais/genética , Ligação Proteica , Proteínas de Protozoários/genética , Trypanosoma brucei brucei/genética , Trypanosoma brucei brucei/crescimento & desenvolvimento
13.
Elife ; 62017 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-29120328

RESUMO

As more people live longer, age-related neurodegenerative diseases are an increasingly important societal health issue. Treatments targeting specific pathologies such as amyloid beta in Alzheimer's disease (AD) have not led to effective treatments, and there is increasing evidence of a disconnect between traditional pathology and cognitive abilities with advancing age, indicative of individual variation in resilience to pathology. Here, we generated a comprehensive neuropathological, molecular, and transcriptomic characterization of hippocampus and two regions cortex in 107 aged donors (median = 90) from the Adult Changes in Thought (ACT) study as a freely-available resource (http://aging.brain-map.org/). We confirm established associations between AD pathology and dementia, albeit with increased, presumably aging-related variability, and identify sets of co-expressed genes correlated with pathological tau and inflammation markers. Finally, we demonstrate a relationship between dementia and RNA quality, and find common gene signatures, highlighting the importance of properly controlling for RNA quality when studying dementia.


Assuntos
Envelhecimento/patologia , Córtex Cerebral/patologia , Perfilação da Expressão Gênica , Hipocampo/patologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Demência/patologia , Feminino , Humanos , Masculino
14.
J Comp Neurol ; 524(16): 3127-481, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27418273

RESUMO

Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole-brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high-resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and 1,356 large-format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto- and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127-3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.


Assuntos
Anatomia Artística , Encéfalo/anatomia & histologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Proteínas de Neurofilamentos/metabolismo , Parvalbuminas/metabolismo
16.
PLoS One ; 6(9): e24538, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21931744

RESUMO

Radial glia (RG) are primarily embryonic neuroglial progenitors that express Brain Lipid Binding Protein (Blbp a.k.a. Fabp7) and Glial Fibrillary Acidic Protein (Gfap). We used these transcripts to demarcate the distribution of spinal cord radial glia (SCRG) and screen for SCRG gene expression in the Allen Spinal Cord Atlas (ASCA). We reveal that neonatal and adult SCRG are anchored in a non-ventricular niche at the spinal cord (SC) pial boundary, and express a "signature" subset of 122 genes, many of which are shared with "classic" neural stem cells (NSCs) of the subventricular zone (SVZ) and SC central canal (CC). A core expressed gene set shared between SCRG and progenitors of the SVZ and CC is particularly enriched in genes associated with human disease. Visualizing SCRG in a Fabp7-EGFP reporter mouse reveals an extensive population of SCRG that extend processes around the SC boundary and inwardly (through) the SC white matter (WM), whose abundance increases in a gradient from cervical to lumbar SC. Confocal analysis of multiple NSC-enriched proteins reveals that postnatal SCRG are a discrete and heterogeneous potential progenitor population that become activated by multiple SC lesions, and that CC progenitors are also more heterogeneous than previously appreciated. Gene ontology analysis highlights potentially unique regulatory pathways that may be further manipulated in SCRG to enhance repair in the context of injury and SC disease.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Neuroglia/patologia , Medula Espinal/patologia , Células-Tronco/citologia , Animais , Doenças Autoimunes/patologia , Encefalomielite/metabolismo , Proteína 7 de Ligação a Ácidos Graxos , Proteínas de Ligação a Ácido Graxo/metabolismo , Perfilação da Expressão Gênica , Proteína Glial Fibrilar Ácida/biossíntese , Proteínas de Fluorescência Verde/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/metabolismo , Neuroglia/citologia , Neuroglia/metabolismo , Fenótipo , Medula Espinal/citologia , Traumatismos da Medula Espinal/patologia
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