scholarly journals Cortical Cartography: Mapping Arealization Using Single-Cell Omics Technology

2021 ◽  
Vol 15 ◽  
Author(s):  
Patricia R. Nano ◽  
Claudia V. Nguyen ◽  
Jessenya Mil ◽  
Aparna Bhaduri
Keyword(s):  
Single Cell ◽  
Gene Networks ◽  
Structural Characteristics ◽  
Computational Power ◽  
Human Cortex ◽  
Modular Network ◽  
New Era ◽  
Omics Technologies ◽  
Cortical Areas ◽  
Cognitive Power

The cerebral cortex derives its cognitive power from a modular network of specialized areas processing a multitude of information. The assembly and organization of these regions is vital for human behavior and perception, as evidenced by the prevalence of area-specific phenotypes that manifest in neurodevelopmental and psychiatric disorders. Generations of scientists have examined the architecture of the human cortex, but efforts to capture the gene networks which drive arealization have been hampered by the lack of tractable models of human neurodevelopment. Advancements in “omics” technologies, imaging, and computational power have enabled exciting breakthroughs into the molecular and structural characteristics of cortical areas, including transcriptomic, epigenomic, metabolomic, and proteomic profiles of mammalian models. Here we review the single-omics atlases that have shaped our current understanding of cortical areas, and their potential to fuel a new era of multi-omic single-cell endeavors to interrogate both the developing and adult human cortex.

scholarly journals Single-cell atlas of early human brain development highlights heterogeneity of human neuroepithelial cells and early radial glia

2021 ◽  
Author(s):  
Ugomma C. Eze ◽  
Aparna Bhaduri ◽  
Maximilian Haeussler ◽  
Tomasz J. Nowakowski ◽  
Arnold R. Kriegstein
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Single Cell ◽  
Radial Glia ◽  
Cortical Development ◽  
Cell Types ◽  
Human Cortex ◽  
Early Stages ◽  
Human Brain Development ◽  
Neuroepithelial Cells

AbstractThe human cortex comprises diverse cell types that emerge from an initially uniform neuroepithelium that gives rise to radial glia, the neural stem cells of the cortex. To characterize the earliest stages of human brain development, we performed single-cell RNA-sequencing across regions of the developing human brain, including the telencephalon, diencephalon, midbrain, hindbrain and cerebellum. We identify nine progenitor populations physically proximal to the telencephalon, suggesting more heterogeneity than previously described, including a highly prevalent mesenchymal-like population that disappears once neurogenesis begins. Comparison of human and mouse progenitor populations at corresponding stages identifies two progenitor clusters that are enriched in the early stages of human cortical development. We also find that organoid systems display low fidelity to neuroepithelial and early radial glia cell types, but improve as neurogenesis progresses. Overall, we provide a comprehensive molecular and spatial atlas of early stages of human brain and cortical development.

scholarly journals Recent Advances in Single-Cell Profiling and Multispecific Therapeutics: Paving the Way for a New Era of Precision Medicine Targeting Cardiac Fibroblasts

2021 ◽  
Vol 23 (7) ◽  
Author(s):  
Sally Yu Shi ◽  
Xin Luo ◽  
Tracy M. Yamawaki ◽  
Chi-Ming Li ◽  
Brandon Ason ◽  
...  
Keyword(s):  
Heart Failure ◽  
Precision Medicine ◽  
Single Cell ◽  
Cardiac Fibroblasts ◽  
Rapid Development ◽  
Cardiac Fibroblast ◽  
New Era ◽  
Fibroblast Activation ◽  
Cell Gene Expression ◽  
The Way

Abstract Purpose of Review Cardiac fibroblast activation contributes to fibrosis, maladaptive remodeling and heart failure progression. This review summarizes the latest findings on cardiac fibroblast activation dynamics derived from single-cell transcriptomic analyses and discusses how this information may aid the development of new multispecific medicines. Recent Findings Advances in single-cell gene expression technologies have led to the discovery of distinct fibroblast subsets, some of which are more prevalent in diseased tissue and exhibit temporal changes in response to injury. In parallel to the rapid development of single-cell platforms, the advent of multispecific therapeutics is beginning to transform the biopharmaceutical landscape, paving the way for the selective targeting of diseased fibroblast subpopulations. Summary Insights gained from single-cell technologies reveal critical cardiac fibroblast subsets that play a pathogenic role in the progression of heart failure. Combined with the development of multispecific therapeutic agents that have enabled access to previously “undruggable” targets, we are entering a new era of precision medicine.

Computational Exploration of Functional Nanoscale Carbonaceous Materials

2021 ◽  
Vol 17 ◽  
Author(s):  
Grigoriy Sereda ◽  
Md Tusar Uddin ◽  
Jacob Wente
Keyword(s):  
Biomedical Applications ◽  
Chemical Processes ◽  
Computational Power ◽  
Carbonaceous Materials ◽  
New Materials ◽  
New Era ◽  
Physico Chemical ◽  
Computational Exploration ◽  
Properties Of Materials ◽  
Computational Research

Background: The unique ability of carbon to form a wide variety of allotrope modifications has ushered a new era in the material science. Tuning the properties of these materials by functionalization is a must-have tool for their design customized for a specific practical use. The exponentially growing computational power available to researchers allows for the prediction and thorough understanding of the underlying physico-chemical processes responsible for the practical properties of pristine and modified carbons using the methods of quantum chemistry. Method: This review focuses on the computational assessment of the influence of functionalization on the properties of carbons and enabling desired practical properties of the new materials. The first section of each part of this review focuses on graphene - nearly planar units built from sp2-carbons. The second section discusses patterns of sp2-carbons rolled-up into curved 3D-structures in a variety of ways (fullerenes). The overview of other types of carbonaceous materials including those with a high abundance of sp3-carbons, including nanodiamonds, can be found in the third section of each manuscript’s part. Conclusion: The computational methods are especially critical for predicting electronic properties of materials such as the band gap, conductivity, optical and photoelectronic properties, solubility, adsorptivity, potential for catalysis, sensing, imaging and biomedical applications. We expect that introduction of defects to carbonaceous materials as a type of their functionalization will be a point of growth in this area of computational research.

scholarly journals Single cell transcriptomics reveal temporal dynamics of critical regulators of germ cell fate during mouse sex determination

2019 ◽  
Author(s):  
Chloé Mayère ◽  
Yasmine Neirijnck ◽  
Pauline Sararols ◽  
Chris M Rands ◽  
Isabelle Stévant ◽  
...  
Keyword(s):  
Sex Determination ◽  
Germ Cell ◽  
Single Cell ◽  
Cell Fate ◽  
Gene Networks ◽  
Network Inference ◽  
Temporal Dynamics ◽  
Intron Retention ◽  
Gonad Development ◽  
Altered Expression

SummaryDespite the importance of germ cell (GC) differentiation for sexual reproduction, the gene networks underlying their fate remain unclear. Here, we comprehensively characterize the gene expression dynamics during sex determination based on single-cell RNA sequencing of 14,914 XX and XY mouse GCs between embryonic days (E) 9.0 and 16.5. We found that XX and XY GCs diverge transcriptionally as early as E11.5 with upregulation of genes downstream of the Bone morphogenic protein (BMP) and Nodal/Activin pathways in XY and XX GCs, respectively. We also identified a sex-specific upregulation of genes associated with negative regulation of mRNA processing and an increase in intron retention consistent with a reduction in mRNA splicing in XY testicular GCs by E13.5. Using computational gene regulation network inference analysis, we identified sex-specific, sequential waves of putative key regulator genes during GC differentiation and revealed that the meiotic genes are regulated by positive and negative master modules acting in an antagonistic fashion. Finally, we found that rare adrenal GCs enter meiosis similarly to ovarian GCs but display altered expression of master genes controlling the female and male genetic programs, indicating that the somatic environment is important for GC function. Our data is available on a web platform and provides a molecular roadmap of GC sex determination at single-cell resolution, which will serve as a valuable resource for future studies of gonad development, function and disease.

scholarly journals Critical changes in hypothalamic gene networks in response to pancreatic cancer as found by single-cell RNA sequencing

2022 ◽  
pp. 101441
Author(s):  
Christian Huisman ◽  
Mason A. Norgard ◽  
Peter R. Levasseur ◽  
Stephanie M. Krasnow ◽  
Monique G.P. van der Wijst ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Single Cell ◽  
Rna Sequencing ◽  
Gene Networks ◽  
Single Cell Rna Sequencing

scholarly journals Single-cell sequencing leads a new era of profiling transcriptomic landscape

2018 ◽  
Vol 1 (1) ◽  
pp. 2-6 ◽  
Author(s):  
Huidan Zhang ◽  
Naiwen Cui ◽  
Yamei Cai ◽  
Fengyang Lei ◽  
David A. Weitz
Keyword(s):  
Single Cell ◽  
New Era ◽  
Single Cell Sequencing

Sequential glycan profiling at single cell level with the microfluidic lab-in-a-trench platform: a new era in experimental cell biology

Lab on a Chip ◽  
2014 ◽  
Vol 14 (18) ◽  
pp. 3629-3639 ◽  
Author(s):  
Tríona M. O'Connell ◽  
Damien King ◽  
Chandra K. Dixit ◽  
Brendan O'Connor ◽  
Dermot Walls ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Biology ◽  
Single Cell Level ◽  
Cell Level ◽  
New Era ◽  
Experimental Cell ◽  
A Cell ◽  
Glycan Profiling

It is now widely recognised that the earliest changes that occur on a cell when it is stressed or becoming diseased are alterations in its surface glycosylation.

scholarly journals Epigenomic convergence of genetic and immune risk factors in neurodevelopmental disorder cortex

2018 ◽  
Author(s):  
Vogel Ciernia A. ◽  
Laufer B.I. ◽  
Dunaway K.W. ◽  
Hwang H. ◽  
Mordaunt C.E. ◽  
...  
Keyword(s):  
Risk Factors ◽  
Gene Networks ◽  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Cell Types ◽  
Developed Countries ◽  
Autism Spectrum ◽  
Regulatory Regions ◽  
Human Cortex ◽  
Genes And Environment

AbstractNeurodevelopmental disorders (NDDs) impact 7% to 14% of all children in developed countries and are one of the leading causes of lifelong disability. Epigenetic modifications are poised at the interface between genes and environment and are predicted to reveal insight into the gene networks, cell types, and developmental timing of NDD etiology. Whole-genome bisulfite sequencing was used to examine DNA methylation in 49 human cortex samples from three different NDDs (autism spectrum disorder, Rett syndrome, and Dup15q syndrome) and matched controls. Integration of methylation differences across NDDs with relevant genomic and genetic datasets revealed differentially methylated regions (DMRs) unique to each type of NDD but with shared regulatory functions in neurons and microglia. DMRs were significantly enriched for known NDD genetic risk factors, including both common inherited and rare de novo variants. Weighted region co-methylation network analysis revealed a module related to NDD diagnosis and enriched for microglial regulatory regions. Together, these results demonstrate an epigenomic signature of NDDs in human cortex shared with known genetic and immune etiological risk. Epigenomic insights into cell types and gene regulatory regions will aid in defining therapeutic targets and early biomarkers at the interface of genetic and environmental NDD risk factors.

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