scholarly journals Tracing cortical circuits in humans and non-human primates from high resolution connectomic, transcriptomic, and temporal dimensions

2021 ◽  
Author(s):  
Christine J. Charvet ◽  
Kwadwo Ofori ◽  
Christine Baucum ◽  
Jianli Sun ◽  
Melinda S. Modrell ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Resolution ◽  
Human Brain ◽  
Frontal Cortex ◽  
Neural Circuits ◽  
Human Cognition ◽  
Biological Organization ◽  
Brain Connectome ◽  
Temporal Dimensions ◽  
Human Primate

AbstractThe neural circuits that support human cognition are a topic of enduring interest. Yet, the lack of tools available to map human brain circuits has precluded our ability to trace the human and non-human primate connectome. We harnessed high-resolution connectomic, anatomic, and transcriptomic data to investigate the evolution and development of frontal cortex circuitry. We applied machine learning to RNA sequencing data to find corresponding ages between humans and macaques and to compare the development of circuits across species. We transcriptionally defined neural circuits by testing for associations between gene expression and white matter maturation. We then considered transcriptional and structural growth to test whether frontal cortex circuit maturation is unusually extended in humans relative to other species. We also considered gene expression and high-resolution diffusion MR tractography of adult brains to test for cross-species variation in frontal cortex circuits. We found that frontal cortex circuitry development is extended in primates, and concomitant with an expansion in cortico-cortical pathways compared with mice in adulthood. Importantly, we found that these parameters varied relatively little across humans and studied primates. These data identify a surprising collection of conserved features in frontal cortex circuits across humans and Old World monkeys. Our work demonstrates that integrating transcriptional and connectomic data across temporal dimensions is a robust approach to trace the evolution of brain connectomics in primates.Significance StatementWe lack appropriate tools to visualize the human brain connectome. We develop new approaches to study connections in the human and non-human primate brains. The integration of transcription with structure offers an unprecedented opportunity to study circuitry evolution. Our integrative approach finds corresponding ages across species and transcriptionally defines neural circuits. We used this information to test for variation in circuit maturation across species and found a surprising constellation of similar features in frontal cortex neural circuits across humans and primates. Integrating across scales of biological organization expands the repertoire of tools available to study connections in primates, which opens new avenues to study connections in health and diseases of the human brain.

scholarly journals Cutting across structural and transcriptomic scales translates time across the lifespan and resolves frontal cortex development in human evolution

2020 ◽  
Author(s):  
Christine J. Charvet
Keyword(s):  
Prefrontal Cortex ◽  
Human Brain ◽  
Temporal Variation ◽  
Frontal Cortex ◽  
Human Cognition ◽  
Developmental Programs ◽  
Rigorous Approach ◽  
Expression Of Genes ◽  
Transcriptional Variation ◽  
Development And Aging

AbstractHow the unique capacities of human cognition arose in evolution is a question of enduring interest. It is still unclear which developmental programs are responsible for the emergence of the human brain. The inability to determine corresponding ages between humans and apes has hampered progress in detecting developmental programs leading to the emergence of the human brain. I harness temporal variation in anatomical, behavioral, and transcriptional variation to determine corresponding ages from fetal to postnatal development and aging, between humans and chimpanzees. This multi-dimensional approach results in 137 corresponding time points across the lifespan, from embryonic day 44 to ∼55 years of age, in humans and their equivalent ages in chimpanzees. I used these data to test whether developmental programs, such as the timeline of prefrontal cortex maturation, previously claimed to differ between humans and chimpanzees, do so once variation in developmental schedules is controlled for. I compared the maturation of frontal cortex projections from structural magnetic resonance (MR) scans and from temporal variation in the expression of genes used to track long-range projecting neurons (i.e., supragranular-enirhced genes) in chimpanzees and humans. Contrary to what has been suggested, the timetable of prefrontal cortex maturation is not unusually extended in humans. This dataset, which is the largest with which to determine corresponding ages across humans and chimpanzees, provides a rigorous approach to control for variation in developmental schedules and to identify developmental programs responsible for unique features of the human brain.

scholarly journals A Hybrid CPU-GPU Accelerated Framework for Fast Mapping of High-Resolution Human Brain Connectome

PLoS ONE ◽  
2013 ◽  
Vol 8 (5) ◽  
pp. e62789 ◽  
Author(s):  
Yu Wang ◽  
Haixiao Du ◽  
Mingrui Xia ◽  
Ling Ren ◽  
Mo Xu ◽  
...  
Keyword(s):  
High Resolution ◽  
Human Brain ◽  
Fast Mapping ◽  
Brain Connectome

scholarly journals Correction: A Hybrid CPU-GPU Accelerated Framework for Fast Mapping of High-Resolution Human Brain Connectome

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
Author(s):  
Yu Wang ◽  
Haixiao Du ◽  
Mingrui Xia ◽  
Ling Ren ◽  
Mo Xu ◽  
...  
Keyword(s):  
High Resolution ◽  
Human Brain ◽  
Fast Mapping ◽  
Brain Connectome

scholarly journals Application of Airy beam light sheet microscopy to examine early neurodevelopmental structures in 3D hiPSC-derived human cortical spheroids

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dwaipayan Adhya ◽  
George Chennell ◽  
James A. Crowe ◽  
Eva P. Valencia-Alarcón ◽  
James Seyforth ◽  
...  
Keyword(s):  
High Resolution ◽  
Human Brain ◽  
Light Sheet ◽  
Autism Spectrum ◽  
Model Systems ◽  
Large Field ◽  
Autism Spectrum Conditions ◽  
Patient Specific ◽  
Airy Beam

Abstract Background The inability to observe relevant biological processes in vivo significantly restricts human neurodevelopmental research. Advances in appropriate in vitro model systems, including patient-specific human brain organoids and human cortical spheroids (hCSs), offer a pragmatic solution to this issue. In particular, hCSs are an accessible method for generating homogenous organoids of dorsal telencephalic fate, which recapitulate key aspects of human corticogenesis, including the formation of neural rosettes—in vitro correlates of the neural tube. These neurogenic niches give rise to neural progenitors that subsequently differentiate into neurons. Studies differentiating induced pluripotent stem cells (hiPSCs) in 2D have linked atypical formation of neural rosettes with neurodevelopmental disorders such as autism spectrum conditions. Thus far, however, conventional methods of tissue preparation in this field limit the ability to image these structures in three-dimensions within intact hCS or other 3D preparations. To overcome this limitation, we have sought to optimise a methodological approach to process hCSs to maximise the utility of a novel Airy-beam light sheet microscope (ALSM) to acquire high resolution volumetric images of internal structures within hCS representative of early developmental time points. Results Conventional approaches to imaging hCS by confocal microscopy were limited in their ability to image effectively into intact spheroids. Conversely, volumetric acquisition by ALSM offered superior imaging through intact, non-clarified, in vitro tissues, in both speed and resolution when compared to conventional confocal imaging systems. Furthermore, optimised immunohistochemistry and optical clearing of hCSs afforded improved imaging at depth. This permitted visualization of the morphology of the inner lumen of neural rosettes. Conclusion We present an optimized methodology that takes advantage of an ALSM system that can rapidly image intact 3D brain organoids at high resolution while retaining a large field of view. This imaging modality can be applied to both non-cleared and cleared in vitro human brain spheroids derived from hiPSCs for precise examination of their internal 3D structures. This process represents a rapid, highly efficient method to examine and quantify in 3D the formation of key structures required for the coordination of neurodevelopmental processes in both health and disease states. We posit that this approach would facilitate investigation of human neurodevelopmental processes in vitro.

scholarly journals Diffusion MRI microstructure models with in vivo human brain Connectome data: results from a multi-group comparison

2017 ◽  
Vol 30 (9) ◽  
pp. e3734 ◽  
Author(s):  
Uran Ferizi ◽  
Benoit Scherrer ◽  
Torben Schneider ◽  
Mohammad Alipoor ◽  
Odin Eufracio ◽  
...  
Keyword(s):  
Human Brain ◽  
Diffusion Mri ◽  
Group Comparison ◽  
Brain Connectome

scholarly journals Chromatin loop anchors contain core structural components of the gene expression machinery in maize

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Stéphane Deschamps ◽  
John A. Crow ◽  
Nadia Chaidir ◽  
Brooke Peterson-Burch ◽  
Sunil Kumar ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Resolution ◽  
Transcriptional Activity ◽  
Spatial Organization ◽  
Regulatory Elements ◽  
Open Chromatin ◽  
Maize Genome ◽  
Chromatin Loop ◽  
Structural Components ◽  
Chromatin Loops

Abstract Background Three-dimensional chromatin loop structures connect regulatory elements to their target genes in regions known as anchors. In complex plant genomes, such as maize, it has been proposed that loops span heterochromatic regions marked by higher repeat content, but little is known on their spatial organization and genome-wide occurrence in relation to transcriptional activity. Results Here, ultra-deep Hi-C sequencing of maize B73 leaf tissue was combined with gene expression and open chromatin sequencing for chromatin loop discovery and correlation with hierarchical topologically-associating domains (TADs) and transcriptional activity. A majority of all anchors are shared between multiple loops from previous public maize high-resolution interactome datasets, suggesting a highly dynamic environment, with a conserved set of anchors involved in multiple interaction networks. Chromatin loop interiors are marked by higher repeat contents than the anchors flanking them. A small fraction of high-resolution interaction anchors, fully embedded in larger chromatin loops, co-locate with active genes and putative protein-binding sites. Combinatorial analyses indicate that all anchors studied here co-locate with at least 81.5% of expressed genes and 74% of open chromatin regions. Approximately 38% of all Hi-C chromatin loops are fully embedded within hierarchical TAD-like domains, while the remaining ones share anchors with domain boundaries or with distinct domains. Those various loop types exhibit specific patterns of overlap for open chromatin regions and expressed genes, but no apparent pattern of gene expression. In addition, up to 63% of all unique variants derived from a prior public maize eQTL dataset overlap with Hi-C loop anchors. Anchor annotation suggests that < 7% of all loops detected here are potentially devoid of any genes or regulatory elements. The overall organization of chromatin loop anchors in the maize genome suggest a loop modeling system hypothesized to resemble phase separation of repeat-rich regions. Conclusions Sets of conserved chromatin loop anchors mapping to hierarchical domains contains core structural components of the gene expression machinery in maize. The data presented here will be a useful reference to further investigate their function in regard to the formation of transcriptional complexes and the regulation of transcriptional activity in the maize genome.

scholarly journals Uncovering Statistical Links Between Gene Expression and Structural Connectivity Patterns in the Mouse Brain

2021 ◽  
Author(s):  
Nestor Timonidis ◽  
Alberto Llera ◽  
Paul H. E. Tiesinga
Keyword(s):  
Gene Expression ◽  
Mouse Brain ◽  
Structural Connectivity ◽  
Enrichment Analysis ◽  
Underlying Mechanism ◽  
Synaptic Function ◽  
Reticular Nucleus ◽  
Sources Of Information ◽  
Independent Components ◽  
Brain Connectome

AbstractFinding links between genes and structural connectivity is of the utmost importance for unravelling the underlying mechanism of the brain connectome. In this study we identify links between the gene expression and the axonal projection density in the mouse brain, by applying a modified version of the Linked ICA method to volumetric data from the Allen Institute for Brain Science for identifying independent sources of information that link both modalities at the voxel level. We performed separate analyses on sets of projections from the visual cortex, the caudoputamen and the midbrain reticular nucleus, and we determined those brain areas, injections and genes that were most involved in independent components that link both gene expression and projection density data, while we validated their biological context through enrichment analysis. We identified representative and literature-validated cortico-midbrain and cortico-striatal projections, whose gene subsets were enriched with annotations for neuronal and synaptic function and related developmental and metabolic processes. The results were highly reproducible when including all available projections, as well as consistent with factorisations obtained using the Dictionary Learning and Sparse Coding technique. Hence, Linked ICA yielded reproducible independent components that were preserved under increasing data variance. Taken together, we have developed and validated a novel paradigm for linking gene expression and structural projection patterns in the mouse mesoconnectome, which can power future studies aiming to relate genes to brain function.

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