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/genéticaRESUMO
We developed a high-throughput mass spectrometry-based method to simultaneously quantify numerous small-molecule thiols and disulfides in blood plasma. Application of this assay to analyze plasma from patients with known oxidative stress (sickle cell disease and sepsis) and from a patient with sickle cell disease treated with the antioxidant N-acetylcysteine suggests that cysteine disulfides, in particular protein-bound cysteine, serve as sensitive plasma biomarkers for the extent of oxidative stress and effectiveness of antioxidant treatment.