Dataset Information

Molecular and cellular reorganization of neural circuits in the human lineage.

ABSTRACT: To better understand the molecular and cellular differences in brain organization between human and nonhuman primates, we performed transcriptome sequencing of 16 regions of adult human, chimpanzee, and macaque brains. Integration with human single-cell transcriptomic data revealed global, regional, and cell-type-specific species expression differences in genes representing distinct functional categories. We validated and further characterized the human specificity of genes enriched in distinct cell types through histological and functional analyses, including rare subpallial-derived interneurons expressing dopamine biosynthesis genes enriched in the human striatum and absent in the nonhuman African ape neocortex. Our integrated analysis of the generated data revealed diverse molecular and cellular features of the phylogenetic reorganization of the human brain across multiple levels, with relevance for brain function and disease.

SUBMITTER: Sousa AMM

PROVIDER: S-EPMC5776074 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Molecular and cellular reorganization of neural circuits in the human lineage.

Sousa André M M AMM Zhu Ying Y Raghanti Mary Ann MA Kitchen Robert R RR Onorati Marco M Tebbenkamp Andrew T N ATN Stutz Bernardo B Meyer Kyle A KA Li Mingfeng M Kawasawa Yuka Imamura YI Liu Fuchen F Perez Raquel Garcia RG Mele Marta M Carvalho Tiago T Skarica Mario M Gulden Forrest O FO Pletikos Mihovil M Shibata Akemi A Stephenson Alexa R AR Edler Melissa K MK Ely John J JJ Elsworth John D JD Horvath Tamas L TL Hof Patrick R PR Hyde Thomas M TM Kleinman Joel E JE Weinberger Daniel R DR Reimers Mark M Lifton Richard P RP Mane Shrikant M SM Noonan James P JP State Matthew W MW Lein Ed S ES Knowles James A JA Marques-Bonet Tomas T Sherwood Chet C CC Gerstein Mark B MB Sestan Nenad N

Science (New York, N.Y.) 20171101 6366

To better understand the molecular and cellular differences in brain organization between human and nonhuman primates, we performed transcriptome sequencing of 16 regions of adult human, chimpanzee, and macaque brains. Integration with human single-cell transcriptomic data revealed global, regional, and cell-type-specific species expression differences in genes representing distinct functional categories. We validated and further characterized the human specificity of genes enriched in distinct ...[more]

PMID: 29170230

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Project description:Zika virus (ZIKV) is an enveloped positive stranded RNA virus belonging to the genus Flavivirus in the family Flaviviridae that emerged in recent decades causing pandemic outbreaks of human infections occasionally associated with severe neurological disorders in adults and newborns. The intracellular steps of flavivirus multiplication are associated to cellular membranes and their bound organelles leading to an extensive host cell reorganization. Importantly, the association of organelle dysfunction with diseases caused by several human viruses has been widely reported in recent studies. With the aim to increase the knowledge about the impact of ZIKV infection on the host cell functions, the present study was focused on the evaluation of the reorganization of three cell components, promyelocytic leukemia nuclear bodies (PML-NBs), mitochondria, and lipid droplets (LDs). Relevant human cell lines including neural progenitor cells (NPCs), hepatic Huh-7, and retinal pigment epithelial (RPE) cells were infected with the Argentina INEVH116141 ZIKV strain and the organelle alterations were studied by using fluorescent cell imaging analysis. Our results have shown that these three organelles are targeted and structurally modified during ZIKV infection. Considering the nuclear reorganization, the analysis by confocal microscopy of infected cells showed a significantly reduced number of PML-NBs in comparison to uninfected cells. Moreover, a mitochondrial morphodynamic perturbation with an increased fragmentation and the loss of mitochondrial membrane potential was observed in ZIKV infected RPE cells. Regarding lipid structures, a decrease in the number and volume of LDs was observed in ZIKV infected cells. Given the involvement of these organelles in host defense processes, the reported perturbations may be related to enhanced virus replication through protection from innate immunity. The understanding of the cellular remodeling will enable the design of new host-targeted antiviral strategies.

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Molecular and cellular reorganization of neural circuits in the human lineage.

Publications

Molecular and cellular reorganization of neural circuits in the human lineage.

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