scholarly journals Sex differences in gene expression in the human fetal brain

2018 ◽  
Author(s):  
Heath E. O’Brien ◽  
Eilis Hannon ◽  
Aaron R. Jeffries ◽  
William Davies ◽  
Matthew J. Hill ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
Human Brain ◽  
Brain Development ◽  
Developmental Disorders ◽  
Fetal Brain ◽  
Human Fetal Brain ◽  
Human Brain Development ◽  
Early Human ◽  
Sex Biases

ABSTRACTWidespread structural, chemical and molecular differences have been reported between the male and female human brain. Although several neurodevelopmental disorders are more commonly diagnosed in males, little is known regarding sex differences in early human brain development. Here, we used RNA sequencing data from a large collection of human brain samples from the second trimester of gestation (N = 120) to assess sex biases in gene expression within the human fetal brain. In addition to 43 genes (102 Ensembl transcripts) transcribed from the Y-chromosome in males, we detected sex differences in the expression of 2558 autosomal genes (2723 Ensembl transcripts) and 155 genes on the X-chromosome (207 Ensembl transcripts) at a false discovery rate (FDR) < 0.1. Genes exhibiting sex-biased expression in human fetal brain are enriched for high-confidence risk genes for autism and other developmental disorders. Male-biased genes are enriched for expression in neural progenitor cells, whereas female-biased genes are enriched for expression in Cajal-Retzius cells and glia. All gene- and transcript-level data are provided as an online resource (available at http://fgen.psycm.cf.ac.uk/FBSeq1) through which researchers can search, download and visualize data pertaining to sex biases in gene expression during early human brain development.

scholarly journals One-stop Microfluidic Assembly of Human Brain Organoids to Model Prenatal Cannabis Exposure

2020 ◽  
Author(s):  
Zheng Ao ◽  
Hongwei Cai ◽  
Daniel J Havert ◽  
Zhuhao Wu ◽  
Zhiyi Gong ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Developmental Disorders ◽  
Embryonic Stem ◽  
Microfluidic Platform ◽  
Cell Culture Techniques ◽  
Human Brain Development ◽  
One Stop ◽  
On Chip ◽  
Early Human

AbstractPrenatal cannabis exposure (PCE) influences human brain development, but it is challenging to model PCE using animals and current cell culture techniques. Here, we developed a one-stop microfluidic platform to assemble and culture human cerebral organoids from human embryonic stem cells (hESC) to investigate the effect of PCE on early human brain development. By incorporating perfusable culture chambers, air-liquid interface, and one-stop protocol, this microfluidic platform can simplify the fabrication procedure, and produce a large number of organoids (169 organoids per 3.5 cm x 3.5 cm device area) without fusion, as compared with conventional fabrication methods. These one-stop microfluidic assembled cerebral organoids not only recapitulate early human brain structure, biology, and electrophysiology but also have minimal size variation and hypoxia. Under on-chip exposure to the psychoactive cannabinoid, delta-9-tetrahydrocannabinol (THC), cerebral organoids exhibited reduced neuronal maturation, downregulation of cannabinoid receptor type 1 (CB1) receptors, and impaired neurite outgrowth. Moreover, transient on-chip THC treatment also decreased spontaneous firing in microfluidic assembled brain organoids. This one-stop microfluidic technique enables a simple, scalable, and repeatable organoid culture method that can be used not only for human brain organoids, but also for many other human organoids including liver, kidney, retina, and tumor organoids. This technology could be widely used in modeling brain and other organ development, developmental disorders, developmental pharmacology and toxicology, and drug screening.

scholarly journals Exploring early human brain development with structural and physiological neuroimaging

NeuroImage ◽  
2019 ◽  
Vol 187 ◽  
pp. 226-254 ◽  
Author(s):  
Lana Vasung ◽  
Esra Abaci Turk ◽  
Silvina L. Ferradal ◽  
Jason Sutin ◽  
Jeffrey N. Stout ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Human Brain Development ◽  
Early Human

scholarly journals Coordination of Gene Expression of Arachidonic and Docosahexaenoic Acid Cascade Enzymes during Human Brain Development and Aging

PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e100858 ◽  
Author(s):  
Veronica H. Ryan ◽  
Christopher T. Primiani ◽  
Jagadeesh S. Rao ◽  
Kwangmi Ahn ◽  
Stanley I. Rapoport ◽  
...  
Keyword(s):  
Gene Expression ◽  
Docosahexaenoic Acid ◽  
Human Brain ◽  
Brain Development ◽  
Human Brain Development ◽  
Development And Aging

scholarly journals Comprehensive multi-omics integration identifies differentially active enhancers during human brain development with clinical relevance

2021 ◽  
Author(s):  
Soheil Yousefi ◽  
Ruizhi Deng ◽  
Kristina Lanko ◽  
Eva Medico Salsench ◽  
Anita Nikoncuk ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Human Brain ◽  
Brain Development ◽  
Fetal Brain ◽  
Regulatory Elements ◽  
Developmental Genetics ◽  
Brain Disorders ◽  
Genetic Changes ◽  
Human Brain Development ◽  
Depth Analysis

Background: Non-coding regulatory elements (NCREs), such as enhancers, play a crucial role in gene regulation and genetic aberrations in NCREs can lead to human disease, including brain disorders. The human brain is complex and can be affected by numerous disorders; many of these are caused by genetic changes, but a multitude remain currently unexplained. Understanding NCREs acting during brain development has the potential to shed light on previously unrecognised genetic causes of human brain disease. Despite immense community-wide efforts to understand the role of the non-coding genome and NCREs, annotating functional NCREs remains challenging. Results: Here we performed an integrative computational analysis of virtually all currently available epigenome data sets related to human fetal brain. Our in-depth analysis unravels 39,709 differentially active enhancers (DAEs) that show dynamic epigenomic rearrangement during early stages of human brain development, indicating likely biological function. Many of these DAEs are linked to clinically relevant genes, and functional validation of selected DAEs in cell models and zebrafish confirms their role in gene regulation. Compared to enhancers without dynamic epigenomic rearrangement, these regions are subjected to higher sequence constraints in humans, have distinct sequence characteristics and are bound by a distinct transcription factor landscape. DAEs are enriched for GWAS loci for brain related traits and for genetic variation found in individuals with neurodevelopmental disorders, including autism. Conclusion: Our compendium of high-confidence enhancers will assist in deciphering the mechanism behind developmental genetics of the human brain and will be relevant to uncover missing heritability in human genetic brain disorders.

scholarly journals 5-hydroxymethylcytosine is highly dynamic across human fetal brain development

2017 ◽  
Author(s):  
Helen Spiers ◽  
Eilis Hannon ◽  
Leonard C. Schalkwyk ◽  
Nicholas J. Bray ◽  
Jonathan Mill
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Fetal Brain ◽  
Neuronal Function ◽  
Human Fetal Brain ◽  
Dynamic Changes ◽  
Systematic Analysis ◽  
Dna Hydroxymethylation ◽  
Fetal Brain Development ◽  
Epigenetic Processes

ABSTRACTBackgroundEpigenetic processes play a key role in orchestrating transcriptional regulation during the development of the human central nervous system. We previously described dynamic changes in DNA methylation (5mC) occurring during human fetal brain development, but other epigenetic processes operating during this period have not been extensively explored. Of particular interest is DNA hydroxymethylation (5hmC), a modification that is enriched in the human brain and hypothesized to play an important role in neuronal function, learning and memory. In this study, we quantify 5hmC across the genome of 71 human fetal brain samples spanning 23 to 184 days post-conception.ResultsWe identify widespread changes in 5hmC occurring during human brain development, notable sex-differences in 5hmC in the fetal brain, and interactions between 5mC and 5hmC at specific sites. Finally, we identify loci where 5hmC in the fetal brain is associated with genetic variation.ConclusionsThis study represents the first systematic analysis of dynamic changes in 5hmC across neurodevelopment and highlights the potential importance of this modification in the human brain. A searchable database of our fetal brain 5hmC data is available as a resource to the research community at http://epigenetics.essex.ac.uk/fetalbrain2/.

scholarly journals Comprehensive multi-omics integration identifies differentially active enhancers during human brain development with clinical relevance

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Soheil Yousefi ◽  
Ruizhi Deng ◽  
Kristina Lanko ◽  
Eva Medico Salsench ◽  
Anita Nikoncuk ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Human Brain ◽  
Brain Development ◽  
Fetal Brain ◽  
Regulatory Elements ◽  
Developmental Genetics ◽  
Brain Disorders ◽  
Genetic Changes ◽  
Human Brain Development ◽  
Depth Analysis

Abstract Background Non-coding regulatory elements (NCREs), such as enhancers, play a crucial role in gene regulation, and genetic aberrations in NCREs can lead to human disease, including brain disorders. The human brain is a complex organ that is susceptible to numerous disorders; many of these are caused by genetic changes, but a multitude remain currently unexplained. Understanding NCREs acting during brain development has the potential to shed light on previously unrecognized genetic causes of human brain disease. Despite immense community-wide efforts to understand the role of the non-coding genome and NCREs, annotating functional NCREs remains challenging. Methods Here we performed an integrative computational analysis of virtually all currently available epigenome data sets related to human fetal brain. Results Our in-depth analysis unravels 39,709 differentially active enhancers (DAEs) that show dynamic epigenomic rearrangement during early stages of human brain development, indicating likely biological function. Many of these DAEs are linked to clinically relevant genes, and functional validation of selected DAEs in cell models and zebrafish confirms their role in gene regulation. Compared to enhancers without dynamic epigenomic rearrangement, DAEs are subjected to higher sequence constraints in humans, have distinct sequence characteristics and are bound by a distinct transcription factor landscape. DAEs are enriched for GWAS loci for brain-related traits and for genetic variation found in individuals with neurodevelopmental disorders, including autism. Conclusion This compendium of high-confidence enhancers will assist in deciphering the mechanism behind developmental genetics of human brain and will be relevant to uncover missing heritability in human genetic brain disorders.

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