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Publications (386)
Although lipid biology may play a key role in the pathophysiology of mental health disorders such as schizophrenia (SCZ) and bipolar disorder (BD), the nature of this interplay and how it could shape phenotypic presentation, including cognitive performance is still incompletely understood. To address this question, we analyzed the association of pl...
Understanding the molecular basis of the structural organization of the human brain may shed light on its functional mechanism. We present spatial lipidomics analysis of human brain sections containing neocortical gray matter and two white matter regions representing two axonal tracks: the cingulum bundle and the corpus callosum. Using matrix‐assis...
Numerous brain imaging studies have reported white matter alterations in schizophrenia, but the lipidome analysis of the corresponding tissue remains incomplete. In this study, we investigated the lipidome composition of six subcortical white matter regions corresponding to major axonal tracks in both control subjects and schizophrenia patients. Al...
Background
Anxiety and depression significantly contribute to the overall burden of mental disorders, with depression being one of the leading causes of disability. Despite this, no biochemical test has been implemented for the diagnosis of these mental disorders, while recent studies have highlighted lipids as potential biomarkers.
Methods
Using...
BACKGROUND: Schizophrenia is a psychiatric disorder known to affect brain structure and functionality. Structural changes in the brain at the level of gross anatomical structures have been fairly well studied, while microstructural changes, especially those associated with changes in the molecular composition of the brain, are still being investiga...
Lipids are the most abundant but poorly explored components of the human brain. Here, we present a lipidome map of the human brain comprising 75 regions, including 52 neocortical ones. The lipidome composition varies greatly among the brain regions, affecting 93% of the 419 analyzed lipids. These differences reflect the brain’s structural character...
This study explores the potential of using multimodal machine learning methods to improve the diagnosis of schizophrenia. The dataset includes functional connectivity matrices from the COBRE fMRI dataset, consisting of 54 patients with schizophrenia and 69 healthy controls, as well as MR morphometry and information on the levels of lipid intensity...
Chromatin architecture regulates gene expression and shapes cellular identity, particularly in neuronal cells. Specifically, polycomb group (PcG) proteins enable establishment and maintenance of neuronal cell type by reorganizing chromatin into repressive domains that limit the expression of fate-determining genes and sustain distinct gene expressi...
The expansion of the neocortex, a hallmark of mammalian evolution1,2, was accompanied by an increase in cerebellar neuron numbers3. However, little is known about the evolution of the cellular programs underlying cerebellum development in mammals. In this study, we generated single-nucleus RNA-sequencing data for ~400,000 cells to trace cerebellum...
Numerous brain imaging studies have reported white matter alterations in schizophrenia, but the lipidome analysis of the corresponding tissue remains incomplete. In this study, we investigated the lipidome composition of six subcortical white matter regions corresponding to major axonal tracks in both control subjects and schizophrenia patients. Al...
Population density is known to affect the health and survival of many species, and is especially important for social animals. In mice, living in crowded conditions results in the disruption of social interactions, chronic stress, and immune and reproductive suppression; however, the underlying mechanisms remain unclear. Here, we investigated the r...
Oleic acid is a monounsaturated fatty acid increasing oil oxidative stability. High content of oleic acid is thus a valuable trait in oilseed crops. Sunflower (Helianthus annuus L.) normally accumulates linoleic acid as a major fatty acid, but a mutant expressing a high oleic phenotype form was previously obtained by chemical mutagenesis and mapped...
Chromatin architecture regulates gene expression and shapes cellular identity, particularly in neuronal cells. Specifically, polycomb group (PcG) proteins enable establishment and maintenance of neuronal cell type by reorganizing chromatin into repressive domains that limit the expression of fate-determining genes and sustain distinct gene expressi...
Population density is known to affect the health and survival of many species, and is especially important for social animals. In mice, living in crowded conditions results in the disruption of social interactions, chronic stress, and immune and reproductive suppression; however, the underlying mechanisms remain unclear. Here, we investigated the r...
The administration of low doses of D2O to living organisms was used for decades for the investigation of metabolic pathways and for the measurement of the turnover rate for specific compounds. Usually, the investigation of the deuterium uptake in lipids is performed by measuring the deuteration level of the palmitic acid residue using GC-MS instrum...
Background
Changes in gene expression levels during brain development are thought to have played an important role in the evolution of human cognition. With the advent of high-throughput sequencing technologies, changes in brain developmental expression patterns, as well as human-specific brain gene expression, have been characterized. However, int...
The testis produces gametes through spermatogenesis and evolves rapidly at both the morphological and molecular level in mammals 1–6 , probably owing to the evolutionary pressure on males to be reproductively successful ⁷ . However, the molecular evolution of individual spermatogenic cell types across mammals remains largely uncharacterized. Here w...
Neuropathic pain is a condition affecting the quality of life of a substantial part of the population, but biomarkers and treatment options are still limited. While this type of pain is caused by nerve damage, in which lipids play key roles, lipidome alterations related to nerve injury remain poorly studied. Here, we assessed blood lipidome alterat...
Oleic acid is a monounsaturated fatty acid increasing oil oxidative stability. High content of oleic acid is thus a valuable trait in oilseed crops. Sunflower ( Helianthus annuus L.) normally accumulates linoleic acid as a major fatty acid, but a mutant expressing a high oleic phenotype form was previously obtained by chemical mutagenesis and mappe...
Tocopherols are the natural lipophilic antioxidants possessing vitamin E activity. The tocopherol complex in plants includes four different forms, namely, α-tocopherol, β-tocopherol, γ-tocopherol, and δ-tocopherol. Importantly, vitamin E activity decreases from α- to δ-tocopherol, while in vitro antioxidant activity in contrast increases in the row...
Tocopherols and oleic acid are components of sunflower oil that protect it against thermooxidation. Tocopherol composition and oleic acid content are under strong genetic control in plants. Thus it is possible to improve conventional breeding by introducing genetic markers of these traits in order to obtain new varieties with altered oil compositio...
IMPORTANCE No clinically applicable diagnostic test exists for severe mental disorders. Lipids harbor potential as disease markers.
OBJECTIVE To define a reproducible profile of lipid alterations in the blood plasma of patients with schizophrenia (SCZ) independent of demographic and environmental variables and to
investigate its specificity in ass...
Tocopherols are antioxidants that preserve oil lipids against oxidation and serve as a natural source of vitamin E in the human diet. Compared with other major oilseeds like rapeseed and soybean, sunflower (Helianthus annuus L.) exhibits low phenotypic diversity of tocopherol composition, both in wild and cultivated accessions from germplasm collec...
Developmental trajectories of gene expression may reverse in their direction during ageing, a phenomenon previously linked to cellular identity loss. Our analysis of cerebral cortex, lung, liver and muscle transcriptomes of 16 mice, covering development and ageing intervals, revealed widespread but tissue-specific ageing-associated expression rever...
The expansion of the neocortex, one of the hallmarks of mammalian evolution, was accompanied by an increase in the number of cerebellar neurons. However, little is known about the evolution of the cellular programs underlying cerebellum development in mammals. In this study, we generated single-nucleus RNA-sequencing data for ~400,000 cells to trac...
The testis is a key male reproductive organ that produces gametes through the process of spermatogenesis. Testis morphologies and spermatogenesis evolve rapidly in mammals, presumably due to the evolutionary pressure on males to be reproductively successful. The rapid evolution of the testis was shown to be reflected at the molecular level based on...
Fluoxetine is an antidepressant commonly prescribed not only to adults but also to children for the treatment of depression, obsessive-compulsive disorder, and neurodevelopmental disorders. The adverse effects of the long-term treatment reported in some patients, especially in younger individuals, call for a detailed investigation of molecular alte...
Background
Sunflower is an important oilseed crop domesticated in North America approximately 4000 years ago. During the last century, oil content in sunflower was under strong selection. Further improvement of oil properties achieved by modulating its fatty acid composition is one of the main directions in modern oilseed crop breeding.
Results
We...
Alternative splicing (AS) is pervasive in mammalian genomes, yet cross-species comparisons have been largely restricted to adult tissues and the functionality of most AS events remains unclear. We assessed AS patterns across pre- and postnatal development of seven organs in six mammals and a bird. Our analyses revealed that developmentally dynamic...
The relationship between embryonic development and evolution historically investigated based on embryo morphology could now be reassessed using mRNA expression endophenotype. Here, we analyzed the conservation of divergence of the developmental mRNA expression profiles in nine evolutionarily distinct species, from oyster to mouse, and compared them...
We analyze the metabolomes of humans, chimpanzees and macaques in muscle, kidney and three different regions of the brain. Whereas several compounds in amino acid metabolism occur at either higher or lower concentrations in humans than in the other primates, metabolites downstream of adenylosuccinate lyase, which catalyzes two reactions in purine s...
Background
Analysis of lymphocyte cell lines revealed substantial differences in the expression of mRNA and microRNA (miRNA) among human populations. The extent of such population-associated differences in actual human tissues remains largely unexplored. The placenta is one of the few solid human tissues that can be collected in substantial numbers...
Lipidomics is the omics technology aimed to detect and quantify the complete diversity of lipids (lipidome) in the specific sample. Despite numerous reports confirming the crucial role of lipids in the brain functions, studies of brain lipid composition are sparse and incomplete in contrast to genome and transcriptome data. Cerebellum recently emer...
Gene expression tends to reverse its developmental trajectory direction in ageing, a phenomenon previously linked to cellular identity loss. Our analysis of cortex, lung, liver and muscle transcriptomes of 16 mice, covering development and ageing intervals, revealed widespread but tissue-specific ageing-associated expression reversals. Cumulatively...
Mass spectrometry imaging (MSI) has become an important tool for 2D profiling of biological tissues, allowing for the visualization of individual compound distributions in the sample. Based on this information, it is possible to investigate the molecular organization within any particular tissue and detect abnormal regions (such as tumor regions) a...
Background:
Lipids contained in milk are an essential source of energy and structural materials for a growing neonate. Furthermore, lipids' long-chain unsaturated fatty acid residues can directly participate in neonatal tissue formation. Here, we used untargeted mass spectrometric measurements to assess milk lipid composition in seven mammalian sp...
Background: Sunflower is an important oilseed crop domesticated in North America approximately 4000 years ago. During the last century, oil content in sunflower was under strong selection. Further improvement of the oil properties achieved by modulating its fatty acid composition is one of the main directions in modern oilseed crop breeding.
Result...
Lipids are essential to brain functions, yet they remain largely unexplored. Here we investigated the lipidome composition of prefrontal cortex gray matter in 396 cognitively healthy individuals with ages spanning 100 years, as well as 67 adult individuals diagnosed with autism (ASD), schizophrenia (SZ), and Down syndrome (DS). Of the 5024 detected...
The relationship between embryonic development and evolution historically investigated based on embryo morphology, could now be reassessed using mRNA expression endophenotype. Here, we investigated the applicability of von Baer's and Haeckel's arguments at mRNA expression level by comparing the developmental changes among nine evolutionarily distin...
Rapeseed is the second most common oilseed crop worldwide. While the start of rapeseed breeding in Russia dates back to the middle of the 20th century, its widespread cultivation began only recently. In contrast to the world’s rapeseed genetic variation, the genetic composition of Russian rapeseed lines remained unexplored. We have addressed this q...
Background
Analysis of lymphocyte cell lines revealed substantial differences in the expression of mRNA and microRNA (miRNA) among human populations. The extent of such population-associated differences in actual human tissues remains largely unexplored. The placenta is one of the few solid human tissues that can be collected in substantial numbers...
Identification of gene expression traits unique to the human brain sheds light on the molecular mechanisms underlying human evolution. Here, we searched for uniquely human gene expression traits by analyzing 422 brain samples from humans, chimpanzees, bonobos, and macaques representing 33 anatomical regions, as well as 88,047 cell nuclei composing...
We analyze the metabolomes of humans, chimpanzees and macaques in muscle, kidney and three different regions of the brain. Whereas several compounds in amino acid metabolism occur at either higher or lower concentrations in humans than in the other primates, metabolites in oxidative phosphorylation and purine biosynthesis are consistently present i...
Background Lipids contained in breast milk are an essential source of energy and structural materials for a growing infant. Furthermore, lipids’ long-chain unsaturated fatty acid residues can directly participate in infant tissue formation. Here, we used untargeted mass spectrometric measurements to assess breast milk lipid composition in seven mam...
Background Lipids contained in milk are an essential source of energy and structural materials for a growing infant. Furthermore, lipids’ long-chain unsaturated fatty acid residues can directly participate in infant tissue formation. Here, we used untargeted mass spectrometric measurements to assess milk lipid composition in seven mammalian species...
Human populations, despite their overwhelming similarity, contain some distinct phenotypic, genetic, epigenetic, and gene expression features. In this study, we explore population differences at yet another level of molecular phenotype: the abundance of non-polar and polar low molecular weight compounds, lipids and metabolites in the prefrontal cor...
The human brain has undergone substantial change since humans diverged from chimpanzees and the other great apes1,2. However, the genetic and developmental programs that underlie this divergence are not fully understood. Here we have analysed stem cell-derived cerebral organoids using single-cell transcriptomics and accessible chromatin profiling t...
Identification of gene expression traits unique to the human brain sheds light on the mechanisms of human cognition. Here we searched for gene expression traits separating humans from other primates by analyzing 88,047 cell nuclei and 422 tissue samples representing 33 brain regions of humans, chimpanzees, bonobos, and macaques. We show that gene e...
Rapeseed (Brassica napus) is an oilseed crop vastly used to produce vegetable oil for food, chemical, and biofuel industries. Despite the fact that rapeseed is quite popular in terms of trait-genotype association studies the Russian collections which are of high agricultural value remain poorly studied and described. Here we aim to find genetic ass...
The evolution of gene expression in mammalian organ development remains largely uncharacterized. Here we report the transcriptomes of seven organs (cerebrum, cerebellum, heart, kidney, liver, ovary and testis) across developmental time points from early organogenesis to adulthood for human, rhesus macaque, mouse, rat, rabbit, opossum and chicken. C...
The human brain has changed dramatically since humans diverged from our closest living relatives, chimpanzees and the other great apes. However, the genetic and developmental programs underlying this divergence are not fully understood. Here, we have analyzed stem cell-derived cerebral organoids using single-cell transcriptomics (scRNA-seq) and acc...
Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with yet incompletely uncovered molecular determinants. Alterations in the abundance of low molecular weight compounds (metabolites) in ASD could add to our understanding of the disease. Indeed, such alterations take place in the urine, plasma and cerebellum of ASD individuals....
Medawar's mutation accumulation hypothesis explains aging by the declining force of natural selection with age: Slightly deleterious germline mutations expressed in old age can drift to fixation and thereby lead to aging‐related phenotypes. Although widely cited, empirical evidence for this hypothesis has remained limited. Here, we test one of its...
Immediate early genes (IEGs) are useful markers of neuronal activation and essential components of neuronal response. While studies of gastropods have provided many insights into the basic learning and memory mechanisms, the genome-wide assessment of IEGs has been mainly restricted to vertebrates. In this study, we identified IEGs in the terrestria...
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Oilseed crops are one of the most important sources of vegetable oils for food and industry. Nutritional and technical properties of vegetable oil are primarily determined by its fatty acid (FA) composition. The content and composition of FAs in plants are commonly determined using gas chromatography-mass spectrometry (GS-MS) or gas chromatography-...
Significance
Short peptides are encoded in genomes of all organisms and have important functions. Due to the small size of such open reading frames, they are frequently overlooked by automatic genome annotation. We investigated the gene that was misannotated as long noncoding RNA LINC00116 and demonstrated that this gene codes for a 56-amino-acid-l...
The phenomenon of cytoplasmic male sterility (CMS), consisting in the inability to produce functional pollen due to mutations in mitochondrial genome, has been described in more than 150 plant species. With the discovery of nuclear fertility restorer (Rf) genes capable of suppressing the CMS phenotype, it became possible to use the CMS-Rf genetic s...
Oilseed crops are one of the most important sources of vegetable oils for food and industry. Nutritional and technical properties of vegetable oil are primarily determined by its fatty acid (FA) composition. The content and composition of FAs in plants are commonly determined using gas chromatography-mass spectrometry (GS-MS) or gas chromatography-...
Oilseed crops are one of the most important sources of vegetable oils for food and industry. Nutritional and technical properties of vegetable oil are primarily determined by its fatty acid (FA) composition. The content and composition of FAs in plants are commonly determined using gas chromatography-mass spectrometry (GS-MS) or gas chromatography-...
Molecular maps of the human brain alone do not inform us of the features unique to humans. Yet, the identification of these features is important for understanding both the evolution and nature of human cognition. Here, we approached this question by analyzing gene expression and H3K27ac chromatin modification data collected in eight brain regions...
Lipids are essential structural and functional components of cells. Little is known, however, about the evolution of lipid composition in different tissues. Here, we report a large-scale analysis of the lipidome evolution in six tissues of 32 species representing primates, rodents and bats. While changes in genes' sequence and expression accumulate...
MicroRNA (miRNA) sponges are vital components of posttranscriptional gene regulation. Yet, only a limited number of miRNA sponges have been identified. Here, we show that the recently evolved non-coding tumor suppressor transcript, antisense RNA to TP73 gene (TP73-AS1), functions as a natural sponge of human-specific miRNA miR-941. We find unusuall...
Changes in splicing are known to affect the function and regulation of genes. We analyzed splicing events that take place during the postnatal development of the prefrontal cortex in humans, chimpanzees, and rhesus macaques based on data obtained from 168 individuals. Our study revealed that among the 38,822 quantified alternative exons, 15% are di...
Medawar’s mutation accumulation (MA) hypothesis explains ageing by the declining force of natural selection with age: slightly deleterious germline mutations that are functional in old age are not effectively eliminated by selection and therefore lead to ageing-related phenotypes. Although widely cited, empirical support for the MA hypothesis, part...
Maximal lifespan of mammalian species, even if closely related, may differ more than 10-fold, however the nature of the mechanisms that determine this variability is unresolved. Here, we assess the relationship between maximal lifespan duration and concentrations of more than 20,000 lipid compounds, measured in 669 tissue samples from 6 tissues of...
It was previously reported that mRNA expression levels in the prefrontal cortex at old age start to resemble pre-adult levels. Such expression reversals could imply loss of cellular identity in the aging brain, and provide a link between aging-related molecular changes and functional decline. Here we analyzed 19 brain transcriptome age-series datas...
Despite morphological diversification of chordates over 550 million years of evolution, their shared basic anatomical pattern (or 'bodyplan') remains conserved by unknown mechanisms. The developmental hourglass model attributes this to phylum-wide conserved, constrained organogenesis stages that pattern the bodyplan (the phylotype hypothesis); howe...
Although splicing is widespread and evolves rapidly among species, the mechanisms driving this evolution, as well as its functional implications, are not yet fully understood. We analyzed the evolution of splicing patterns based on transcriptome data from five tissues of humans, chimpanzees, rhesus macaques, and mice. In total, 1,526 exons and exon...
Background. Rostral prefrontal cortex, or frontopolar cortex (FPC), also known as Brodmann area 10 (BA10), is the most anterior part of the human brain. It is one of the largest cytoarchitectonic areas of the human brain that has significantly increased its volume during evolution. Anatomically the le (BA10L) and right (BA10R) parts of FPC show sli...
While human cognitive abilities are clearly unique, underlying changes in brain organization and function remain unresolved. Here we characterized the transcriptome of the cortical layers and adjacent white matter in the prefrontal cortexes of humans, chimpanzees and rhesus macaques using unsupervised sectioning followed by RNA sequencing. More tha...
Lipids are essential components of the brain. Here, we conducted a comprehensive mass spectrometry-based analysis of lipidome composition in the prefrontal cortex of 40 humans, 40 chimpanzees, and 40 rhesus monkeys over postnatal development and adulthood. Of the 11,772 quantified lipid peaks, 7,589 change significantly along the lifespan. More tha...
Author Summary
Autism spectrum disorder (ASD) involves disruptions in cognitive functions related to socialization and communication, which are also among the key behavioral capacities that separate humans from other species. This suggests that ASD may involve alterations in evolutionarily novel, human-specific developmental processes. To test this...
Gene expression levels (RPKM values) for all expressed genes.
Genes are shown in rows. The sample group information (h: controls; a: autism cases; c: chimpanzees, m: macaques) and age in days are shown in columns.
(TXT)
Observed and expected gene numbers in Figs 2D, 3C and 4A.
The expected numbers were estimated by 1,000 permutations of cluster labels.
(XLSX)
Profiles of expression changes in autism drawn for different levels of the disease phenotype.
The symbols represent individual expression level measurements (red circles: controls; black stars: autism cases with high ADI-R scores; black triangles: autism cases with moderate ADI-R scores; black crosses: autism cases with low ADI-R scores). The lines...
Gene length distribution in six major clusters of expression changes in autism.
(A) The distribution for all genes in each cluster. (B) The distribution for genes sampled based on cluster 2 gene length distribution.
(PDF)
Distribution of Pearson correlation coefficients between gene expression and H3K4me3 modification differences in autism and control individuals.
The expression difference or modification difference was calculated based on 8 pairs of age-matched autism and control samples in both datasets (S1 Table), with age ranged from 2 to 60 years old. The red l...
Summary of sequence reads in the RNA-seq batch.
(PDF)
Dimensions 1 and 2 from the multidimensional scaling (MDS) of all expressed genes in autism cases and unaffected controls.
(XLSX)
The number and functional enrichment of clusters defined at different height cutoffs of the hierarchical clustering tree.
(A) Hierarchical clustering of 1,775 genes differently expressed between autism cases and controls (the same as on Fig 2A). (B) Number of gene clusters obtained by cutting the hierarchical clustering tree at different heights. C...
Gene clusters determined using log2-transformed RPKM values.
The panels show expression patterns of the seven gene clusters of autism-related genes identified using log2-transformed RPKM values and uniform tree cutting cutoff at 1.4. The x-axis shows the age information on the (age)1/4 scale, the y-axis shows the expression levels standardized to m...
Comparison of clusters based on 1,775 genes differentially expressed in autism (x-axis) and all 12,557 detected genes.
The cells show overlap between genes in six clusters used in main analysis (x-axis) and genes in 48 clusters based on analysis of all 12,557 detected genes using RPKM values and uniform tree cutting cutoff at 1.4 (y-axis). Each cel...
Enriched GO functional terms of cluster 4 (Call_4), overlapping with cluster 2 of the main analysis.
GO functional terms significantly enriched in cluster 4 (Call_4) genes defined based on clustering of all genes detected as expressed in autism and control samples. The enriched functional terms (y-axis) were sorted based on the hypergeometric test...
Overlap between genes associated with autism based on genetic studies and genes in six major clusters of expression changes in autism corrected for length difference as shown in S9 Fig.
The genes associated with autism were collected from: (A) the SFARI AutDB database, (B) the SFARI scored genes, (C) the AutismKB database, (D) four published whole-...
Overlap of autism-related clusters (x-axis) and cell type markers collected from Zeisel et al, 2015 (y-axis).
Each cell shows the number and percentage of overlapping genes; the p-value indicating significance of the overlap calculated using Fisher’s exact test followed by BH correction for multiple testing. The y-axis marker colors represent cell...
Correlation of age-related gene expression change between RNA-seq and microarray datasets.
Shown are the distributions of Pearson correlation coefficients calculated based on expression levels at 15 points interpolated from the cubic spline curves fitted to individual microarray or RNA-seq expression measurements of each species (red: humans, blue:...
