Biology subjects

Xia, Y.

Publications and source records attributed to Xia, Y..

At least 163 records · Page 9Linked to original sources

bioRxiv2022

Genome Enrichment of Rare, Unknown Species from Complicated Microbiome by Nanopore Selective Sequencing

Rare species are vital members of a microbial community, but retrieving their genomes is difficult due to their low abundance. The ReadUntil (RU) approach allows nanopore devices to sequence specific DNA molecules selectively in real-time, which provides an opportunity for enriching rare species. However, there is still a gap in RU-based enriching of rare and unknown species in environmental samples whose community composition is unclear, and many species lack corresponding reference in public databases. Here we present metaRUpore to overcome this challenge. We applied metaRUpore to a thermophilic anaerobic digester (TAD) community, it successfully redirected the sequencing throughput from high-abundance populations to rare species while facilitating the recovery of 41 high-quality metagenome-assembled genomes (MAGs) at low sequencing effort. The simplicity and robustness of the approach make it accessible for labs with moderate computational resources and hold the potential to become the standard practice in future metagenomic sequencing of complicated microbiomes.

bioinformatics↗

bioRxiv2022

Dietary butyrate treatment enhances healthy metabolites by longitudinal untargeted metabolomic analysis in amyotrophic lateral sclerosis mice

Microbial metabolites affect the neuron system and muscle cell functions. Amyotrophic Lateral Sclerosis (ALS) is a multifactorial neuromuscular disease. Our previous study has demonstrated elevated intestinal inflammation and dysfunctional microbiome in ALS patients and an ALS mouse model (human-SOD1G93A transgenic mice). However, the metabolites in ALS progression are unknown. Using an unbiased global metabolomic measurement and targeted measurement, we investigated the longitudinal changes of fecal metabolites in the SOD1G93A mice over the course of 13 weeks. We compared the changes of metabolites and inflammatory response in age-matched WT and SOD1G93A mice treated with bacterial product butyrate. We found changes in carbohydrate levels, amino acid metabolism, and formation of gamma-glutamyl amino acids. Shifts in several microbially-contributed catabolites of aromatic amino acids agree with butyrate-induced changes in composition of gut microbiome. Declines in gamma-glutamyl amino acids in feces may stem from differential expression of GGT in response to butyrate administration. Due to signaling nature of amino acid-derived metabolites, these changes indicate changes in inflammation (e.g. histamine) and contribute to differences in systemic levels of neurotransmitters (e.g. GABA, glutamate). Butyrate treatment was able to restore some of the healthy metabolites in ALS mice. Moreover, microglia in the spinal cord were measured by the IBA1 staining. Butyrate treatment significantly suppressed the IBA1 level in the SOD1G93A mice. The serum IL-17 and LPS were significantly reduced in the butyrate treated SOD1G93A mice. We have demonstrated an inter-organ communications link among metabolites, inflammation, and ALS progression, suggesting the potential to use metabolites as ALS hallmarks and for treatment. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/476456v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@16d3e4dorg.highwire.dtl.DTLVardef@1155c05org.highwire.dtl.DTLVardef@14c6155org.highwire.dtl.DTLVardef@18a30d6_HPS_FORMAT_FIGEXP M_FIG We compared the changes of metabolites and inflammatory response in age-matched WT and SOD1G93A mice treated with bacterial product butyrate. Butyrate treatment was able to restore some of the healthy metabolites in ALS mice. Due to signaling nature of amino acid-derived metabolites, these changes indicate changes in inflammation and contribute to differences in systemic levels of neurotransmitters (e.g. GABA, glutamate). Moreover, butyrate treatment significantly suppressed the microglia IBA1 level and aggregated SOD1G93A in the SOD1G93A mice. The inflammatory cytokine, e.g serum IL-17, was significantly reduced in the butyrate treated SOD1G93A mice. We have demonstrated an inter-organ communications link among metabolites, inflammation, and ALS progression, suggesting the potential to use metabolites as ALS hallmarks and for treatment. C_FIG

physiology↗

bioRxiv2022

Sulfane sulfur post-translationally modifies the global regulator AdpA to influence actinorhodin production and morphological differentiation of Streptomyces coelicolor

The transcription factor AdpA is a key regulator controlling both secondary metabolism and morphological differentiation in Streptomyces. Due to its critical functions, its expression undergoes multi-level regulations at transcriptional, post-transcriptional, and translational levels, yet no post-translational regulation has been reported. Sulfane sulfur, such as organic polysulfide (RSnH, n[≥]2), is common inside microorganisms, but its physiological functions are largely unknown. Herein, we discovered that sulfane sulfur post-translationally modifies AdpA in S. coelicolor via specifically reacting with Cys62 of AdpA to form a persulfide (Cys62-SSH). This modification decreases the affinity of AdpA to its self-promoter PadpA, allowing increased expression of adpA, further promoting the expression of its target genes actII-4 and wblA. ActII-4 activates actinorhodin biosynthesis and WblA regulates morphological development. Bioinformatics analyses indicated that AdpA-Cys62 is highly conserved in Streptomyces, suggesting the prevalence of such modification in this genus. Thus, our study unveils a new type of regulation on the AdpA activity and sheds a light on how sulfane sulfur stimulates the production of antibiotics in Streptomyces. IMPORTANCEStreptomyces produce myriad of polyketide compounds having (potential) clinical applications. While the database of polyketide gene clusters are quickly expanding, the regulation mechanisms of them are rarely known. Sulfane sulfur species are commonly present in microorganisms with unclear functions. Herein, we discovered that sulfane sulfur increases actinorhodin (ACT) production in S. coelicolor. The underlying mechanism is sulfane sulfur specifically reacts with AdpA, a global transcription factor controlling both ACT gene cluster and morphological differentiation related genes, to form sulfhydrated AdpA. This modification changes dynamics of AdpA-controlled gene network and leads to high expression of ACT biosynthetic genes. Given the wide prevalence of AdpA and sulfane sulfur in Streptomyces, this mechanism may represent a common regulating pattern of polyketide gene clusters. Thus, this finding provides a new strategy for mining and activating valuable polyketide gene clusters.

microbiology↗

bioRxiv2021

PERIOD phosphoclusters control temperature compensation of the Drosophila circadian clock

Temperature compensation is a critical feature of circadian rhythms, but how it is achieved remains elusive. Here, we uncovered the important role played by the Drosophila PERIOD (PER) phosphodegron in temperature compensation. Using CRISPR-Cas9, we introduced a series of mutations that altered three Serines (S44, 45 and 47) belonging to the PER phosphodegron, the functional homolog of mammalian PER2s S487 phosphodegron, which impacts temperature compensation. While all three Serine to Alanine substitutions lengthened period at all temperatures tested, temperature compensation was differentially affected. S44A and S45A substitutions caused decreased temperature compensation, while S47A resulted in overcompensation. These results thus reveal unexpected functional heterogeneity of phosphodegron residues in thermal compensation. Furthermore, mutations impairing phosphorylation of the pers phosphocluster decreased thermal compensation, consistent with its inhibitory role on S47 phosphorylation. Interestingly, the S47A substitution caused increased accumulation of hyper-phosphorylated PER at warmer temperatures. This finding was corroborated by cell culture assays in which S47A resulted in excessive temperature compensation of phosphorylation-dependent PER degradation. Thus, we show a novel role of the PER phosphodegron in temperature compensation through temperature-dependent modulation of the abundance of hyper-phosphorylated PER. Our work also reveals interesting mechanistic convergences and differences between mammalian and Drosophila temperature compensation of the circadian clock. Author summaryCircadian rhythms are critical adaptive mechanisms that enable most organisms to adjust their physiology and behavior to the changes that occur in their environment every day. Ambient temperature varies constantly, but interestingly molecular circadian pacemakers do not accelerate with increasing temperature, while most biochemical reactions are sensitive to temperature. This phenomenon of circadian temperature compensation is poorly understood. Using genome editing and transgenic approaches, we found that two phosphorylated motifs in the Drosophila PERIOD protein, which regulate stability, impact temperature compensation. Moreover, we observed that mutation of a key Serine residue controlling PER degradation, S47, affects the accumulation of phosphorylated PER in a temperature-dependent manner, and causes PER degradation kinetics to become overly protected from increased temperature. As a result, the circadian clock of S47 mutant flies is excessively temperature-compensated. Our work thus reveals an interesting mechanism that controls temperature compensation in Drosophila. Moreover, comparison with mammals reveal interesting similarities, but also important differences in how temperature compensation of the circadian clock is achieved.

genetics↗

bioRxiv2021

Human embryos arrest in a quiescent-like state characterized by metabolic and zygotic genome activation problems

Around 60% of in vitro fertilized (IVF) human embryos irreversibly arrest before compaction between the 3-8-cell stage, posing a significant clinical problem. The mechanisms behind this arrest are unclear. Here, we show that the arrested embryos enter a quiescent-like state, marked by cell cycle arrest, the downregulation of ribosomes and histones and downregulation of MYC and p53 activity. Mechanistically, the arrested embryos can be divided into three types. Type I embryos fail to complete the maternal-zygotic transition, and type II/III embryos have erroneously low levels of glycolysis and variable levels of oxidative phosphorylation. Treatment with resveratrol or nicotinamide riboside (NR) can partially rescue the arrested phenotype. The mechanism of reactivation involves the upregulation of SIRT1, and activation of glycolysis and fatty acid oxidation which forces the embryos out of a quiescent state. Overall, our data reveal how human embryo arrest can be overcome by modulating metabolic pathways.

developmental biology↗

bioRxiv2021

Divergent clonal differentiation trajectories of T cell exhaustion

T cells activated by chronic antigen exposure in the setting of viral infections or cancer can adopt an exhausted T cell (Tex) state, characterized by reduced effector function and proliferative capacity, and the upregulation of inhibitory receptors. However, whether all antigen-specific T cell clones follow the same molecular and cellular Tex differentiation trajectory remains unclear. Here, we generate a single-cell multi-omic atlas of T cell exhaustion that redefines the phenotypic diversity and molecular regulation of Tex phenotypes. Longitudinal analysis during chronic viral infection identifies an early effector phenotype that is epigenetically primed for Tex differentiation and two late-stage Tex cell states with either a terminal exhaustion or a killer cell lectin-like receptor (KLR)-expressing cytotoxic gene signature. We define clonal trajectories of antigen-specific T cells using paired single-cell RNA and T cell receptor sequencing and reveal distinct differentiation trajectories resulting in terminal Tex-biased, KLR Tex-biased, or divergent clones that differentiate into both phenotypes. Comparison of Tex phenotypes among shared T cell clones that traffic to multiple organs reveals that clonal differentiation trajectories are maintained across tissues. Finally, we show that differences in clonal differentiation trajectory are driven by TCR signal strength, whereby high-affinity T cell clones preferentially adopt a terminal Tex fate, while low-affinity clones adopt an effector-like KLR Tex fate that is detectable long-term but depleted in high antigen settings. These findings reveal clonal heterogeneity in the T cell response to chronic antigen and genomic programs that underlie Tex fates and persistence. HighlightsO_LIA single-cell atlas of T cell exhaustion identifies novel early effector and KLR Tex states. C_LIO_LIClonal T cell analysis defines divergent differentiation trajectories during chronic viral infection leading to terminal and KLR Tex fates. C_LIO_LIThe heterogeneity of the Tex pool arises from three primary differentiation patterns and are differentially persistent in the setting of high antigen. C_LIO_LIClonal Tex differentiation patterns are conserved across organ sites and driven by TCR signal strength. C_LI

immunology↗

bioRxiv2021

Systematic Interrogation of Protein Refolding Under Cellular-Like Conditions

The journey by which proteins navigate their energy landscapes to their native structures is complex, involving (and sometimes requiring) many cellular factors and processes operating in partnership with a given polypeptide chains intrinsic energy landscape. The cytosolic environment and its complement of chaperones play critical roles in granting proteins safe passage to their native states; however, the complexity of this medium has generally precluded biophysical techniques from interrogating protein folding under cellular-like conditions for single proteins, let alone entire proteomes. Here, we develop a limited-proteolysis mass spectrometry approach paired with an isotope-labeling strategy to globally monitor the structures of refolding E. coli proteins in the cytosolic medium and with the chaperones, GroEL/ES (Hsp60) and DnaK/DnaJ/GrpE (Hsp70/40). GroEL can refold the majority (85%) of the E. coli proteins for which we have data, and is particularly important for restoring acidic proteins and proteins with three to five domains, trends that come to light because our assay measures the structural outcome of the refolding process itself, rather than indirect measures like binding or aggregation. For the most part, DnaK and GroEL refold a similar set of proteins, supporting the view that despite their vastly different structures, these two chaperones both unfold misfolded states, as one mechanism in common. Finally, we identify a cohort of proteins that are intransigent to being refolded with either chaperone. The data support a model in which chaperone-nonrefolders have evolved to fold efficiently once and only once, co-translationally, and remain kinetically trapped in their native conformations.

biophysics↗

bioRxiv2021

TCR-BERT: learning the grammar of T-cell receptors for flexible antigen-binding analyses

The T-cell receptor (TCR) allows T-cells to recognize and respond to antigens presented by infected and diseased cells. However, due to TCRs staggering diversity and the complex binding dynamics underlying TCR antigen recognition, it is challenging to predict which antigens a given TCR may bind to. Here, we present TCR-BERT, a deep learning model that applies self-supervised transfer learning to this problem. TCR-BERT leverages unlabeled TCR sequences to learn a general, versatile representation of TCR sequences, enabling numerous downstream applications. We demonstrate that TCR-BERT can be used to build state-of-the-art TCR-antigen binding predictors with improved generalizability compared to prior methods. TCR-BERT simultaneously facilitates clustering sequences likely to share antigen specificities. It also facilitates computational approaches to challenging, unsolved problems such as designing novel TCR sequences with engineered binding affinities. Importantly, TCR-BERT enables all these advances by focusing on residues with known biological significance. TCR-BERT can be a useful tool for T-cell scientists, enabling greater understanding and more diverse applications, and provides a conceptual framework for leveraging unlabeled data to improve machine learning on biological sequences.

bioinformatics↗

bioRxiv2021

Genome-wide analysis of DNA methylation reveals selection signatures of the grass carp during domestication

With the rapid development of aquaculture, more and more fish species from wild environments are artificially domesticated and cultured. In the process of domestication, the fish develop some adaptations and phenotypic traits, namely selection signatures. However, it is still unclear about the biological process underlying these selection signatures. Here, we used grass carp (Ctenopharyngodon idellus), an aquaculture fish with the largest production worldwide, to detect its selection signatures and investigate the roles of DNA methylation in the emergence of selection signatures during domestication based on whole-genome bisulfite sequencing technology. Our results showed that domesticated grass carp demonstrated four selection signatures, including growth and metabolism, immunity, foraging and learning behaviors, and 38 candidate genes were associated with these traits. 16 of candidate genes, such as IGF-1, GK, GYS1, etc., were found to play major roles in the growth and metabolism. Immunity signature was related to 11 of candidate genes, including MHCI, MHCII, C1QA, etc. The GRM1, TAS1R1 and TAS1R3 genes were essential for the adaptation of domesticated grass carp to commercial feed in artificial rearing condition. The C-FOS, POMC and CBP genes might be responsible for the acquisition of novel feeding habits and contribute to faster growth indirectly by enhancing food intake. These findings would provide new insights to expand our understanding on the role of DNA methylation in shaping physiological phenotypes in fish, and also contribute to efficient breeding of aquaculture stocks and restocking programs.

genetics↗

bioRxiv2021

MPDB: a unified multi-domain protein structure database integrating structural analogue detection

With the development of protein structure prediction methods and biological experimental determination techniques, the structure of single-domain proteins can be relatively easier to be modeled or experimentally solved. However, more than 80% of eukaryotic proteins and 67% of prokaryotic proteins contain multiple domains. Constructing a unified multi-domain protein structure database will promote the research of multi-domain proteins, especially in the modeling of multi-domain protein structures. In this work, we develop a unified multi-domain protein structure database (MPDB). Based on MPDB, we also develop a server with two functional modules: (1) the culling module, which filters the whole MPDB according to input criteria; (2) the detection module, which identifies structural analogues of the full-chain according to the structural similarity between input domain models and the protein in MPDB. The module can discover the potential analogue structures, which will contribute to high-quality multi-domain protein structure modeling.

bioinformatics↗

bioRxiv2021

Constructing the hierarchy of predictive auditory sequences in the marmoset brain

Our brains constantly generate predictions of sensory input that are compared with actual inputs, propagate the prediction-errors through a hierarchy of brain regions, and subsequently update the internal predictions of the world. However, the essential feature of predictive coding, the notion of hierarchical depth and its neural mechanisms, remains largely unexplored. Here, we investigated the hierarchical depth of predictive auditory processing by combining functional magnetic resonance imaging (fMRI) and high-density whole-brain electrocorticography (ECoG) in marmoset monkeys during an auditory local-global paradigm in which the temporal regularities of the stimuli were designed at two hierarchical levels. The prediction-errors and prediction updates were examined as neural responses to auditory mismatches and omissions. Using fMRI, we identified a hierarchical gradient along the auditory pathway: midbrain and sensory regions represented local, short-time-scale predictive processing followed by associative auditory regions, whereas anterior temporal and prefrontal areas represented global, long-time-scale sequence processing. The complementary ECoG recordings confirmed the activations at cortical surface areas and further differentiated the signals of prediction-error and update, which were transmitted via putatively bottom-up {gamma} and top-down {beta} oscillations, respectively. Furthermore, omission responses caused by absence of input, reflecting solely the two levels of prediction signals that are unique to the hierarchical predictive coding framework, demonstrated the hierarchical predictions in the auditory, temporal, and prefrontal areas. Thus, our findings support the hierarchical predictive coding framework, and outline how neural circuits and spatiotemporal dynamics are used to represent and arrange a hierarchical structure of auditory sequences in the marmoset brain.

neuroscience↗

bioRxiv2021

Ligand-induced unfolding mechanism of an RNA G-quadruplex

The cationic porphyrin, TMPyP4, is a well-established DNA G-quadruplex (G4) binding ligand that can stabilize different topologies via multiple binding modes. However, TMPyP4 has completely opposite destabilizing and unwinding effect on RNA G4 structures. The structural mechanisms that mediate RNA G4 unfolding remains unknown. Here, we report on the TMPyP4-induced RNA G4 unfolding mechanism studied by well-tempered metadynamics (WT-MetaD) with supporting biophysical experiments. The simulations predict a two-state mechanism of TMPyP4 interaction via a groove-bound and a top-face bound conformation. The dynamics of TMPyP4 stacking on the top tetrad disrupts Hoogsteen H-bonds between guanine bases resulting in the consecutive TMPyP4 intercalation from top-to-bottom G-tetrads. The results reveal a striking correlation between computational and experimental approaches and validate WT-MetaD simulations as a powerful tool for studying RNA G4-ligand interactions.

biophysics↗

bioRxiv2021

UCHL1 inhibited by A1 astrocytes facilitates aggregates clearance to promote neural stem cells activation after spinal cord injury

Activation of endogenous neural stem cells (NSCs) is critically important for the adult neurogenesis. However, NSC activation is extremely limited after spinal cord injury (SCI). Recent evidence suggests that accumulation of protein aggregates impedes quiescent NSC activation. Here, we found ubiquitin c-terminal hydrolase l-1 (UCHL1), an important deubiquitinating enzyme, functioned to facilitate NSC activation by clearing protein aggregations through ubiquitin-proteasome approach. Upregulation of UCHL1 enhanced NSC proliferation in the spinal cord after injury. Based on protein microarray analysis of SCI cerebrospinal fluid, it is further revealed that C3+ neurotoxic reactive astrocytes negatively regulated UCHL1 and aggresome clearance through C3/C3aR signaling, resulting in reduced capacity of NSC to activate. Furthermore, blockade of reactive astrocytes or C3/C3aR pathway led to enhanced NSC activation post-SCI. Together, this study elucidated a mechanism regulating NSC activation in the adult spinal cord involving the UCHL1-proteasome approach, which may provide potential molecular targets for NSC fate regulation.

neuroscience↗

bioRxiv2021

Accumulation of auranofin in white adipose tissues lowers leptin levels and exerts anti-diabetic effects

Low-grade, sustained inflammation in white adipose tissue (WAT) characterizes obesity and frequently coincides with insulin resistance and type 2 diabetes (T2D). However, pharmacological targeting of WAT inflammation lacks durable therapeutic effects. Through a computational screen, we identified the FDA-approved rheumatoid arthritis drug auranofin is a putative small molecule for obesity treatment. We discovered that allometrically scaled safe auranofin doses homed to WAT and improved insulin sensitivity in obese wild-type mice. Auranofin treatment also normalized other obesity-associated abnormalities, including hepatic steatosis and hyperinsulinemia. Surprisingly, the anti-diabetic effects of auranofin required leptin lowering and beta-adrenergic receptors in WAT. These metabolic benefits of leptin reduction were superior to any immune impacts of auranofin in WAT. Our studies reveal important metabolic properties of anti-inflammatory treatments and contribute to the notion that leptin reduction in the periphery can be accomplished to treat obesity and T2D.

physiology↗

bioRxiv2021

α-/γ-Taxilin are required for centriolar subdistal appendage assembly and microtubule organization

The centrosome, composed of a pair of centrioles (mother and daughter centrioles) and pericentriolar material, is mainly responsible for microtubule nucleation and anchorage in animal cells. The subdistal appendage (SDA) is a centriolar structure located at the subdistal region on the mother centriole, and it functions in microtubule anchorage. However, the molecular composition and detailed structure of SDA remain largely unknown. Here, we identified a-taxilin and r-taxilin as new SDA components, which form a complex via their coiled-coil domains and serve as a new subgroup during SDA hierarchical assembly. Their SDA localization is dependent on ODF2, and -taxilin recruits CEP170 to the SDA. Functional analyses suggest that -taxilin and {gamma}-taxilin are responsible for centrosomal microtubule anchorage during interphase, as well as for proper spindle orientation during metaphase. Altogether, our results shed light on the molecular components and functional understanding of the SDA hierarchical assembly and microtubule organization.

cell biology↗

bioRxiv2021

Identification of enhancer regulatory elements that direct epicardial gene expression during zebrafish heart regeneration

The epicardium is a mesothelial tissue layer that envelops the heart. Cardiac injury activates dynamic gene expression programs in epicardial tissue, which in the case of zebrafish enables subsequent regeneration through paracrine and vascularizing effects. To identify tissue regeneration enhancer elements (TREEs) that control injury-induced epicardial gene expression during heart regeneration, we profiled transcriptomes and chromatin accessibility in epicardial cells purified from regenerating zebrafish hearts. We identified hundreds of candidate TREEs, defined by increased chromatin accessibility of non-coding elements near genes with increased expression during regeneration. Several of these candidate TREEs were incorporated into stable transgenic lines, with 5 of 6 elements directing injury-induced epicardial expression but not ontogenetic epicardial expression in hearts of larval animals. Whereas two independent TREEs linked to the gene gnai3 showed similar functional features of gene regulation in transgenic lines, two independent ncam1a-linked TREEs directed distinct spatiotemporal domains of epicardial gene expression. Thus, multiple TREEs linked to a regeneration gene can possess either matching or complementary regulatory controls. Our study provides a new resource and principles for understanding the regulation of epicardial genetic programs during heart regeneration.

developmental biology↗

bioRxiv2021

BCL6-dependent TCF-1+ progenitor cells maintain effector and helper CD4 T cell responses to persistent antigen

Shortly after priming, the fate of activated CD4 T cells is segregated into BCL6+ follicular helper T (Tfh) and BCL6- effector (Teff) cells. However, it remains unknown how these subsets are sustained in the presence of chronic antigen stimulation. Using a combination of single cell- and population-based approaches, we show that in chronic viral infection, activated CD4 T cells differentiate into BCL6-dependent TCF-1+ progenitor cells with superior capacity to expand and give rise to both Teff and Tfh. They share properties with progenitor-exhausted CD8 T cells and are required for the continued generation of Teff cells as antigen persists. In response to tumors, an analogous CD4 T cell population develops in draining lymph nodes. Our study reveals the heterogeneity and plasticity of CD4 T cells upon encountering persistent antigen and highlights their population dynamics through a stable bipotent intermediate state.

immunology↗

bioRxiv2021

Development of Functional Connectome Gradients during Childhood and Adolescence

Connectome mapping studies have documented a principal primary-to-transmodal gradient in the adult brain network, capturing a functional spectrum which ranges from perception and action to abstract cognition. However, how this gradient pattern develops and whether its development is linked to cognitive growth, topological reorganization, and gene expression profiles remain largely unknown. Using longitudinal resting-state functional magnetic resonance imaging data from 305 children (ages 6-14), we describe substantial changes in the primary-to-transmodal gradient between childhood and adolescence, including emergence as the principal gradient, expansion of global topography, and focal tuning in primary and default-mode regions. These gradient changes are mediated by developmental changes in network integration and segregation, and are associated with abstract processing functions such as working memory and expression levels of calcium ion regulated exocytosis, synaptic transmission, and axon and synapse part related genes. Our findings have implications for understanding connectome maturation principles in normal development and developmental disorders. TeaserOur study reported the maturation of the core connectome gradient and its association with cognitions and genes expression.

neuroscience↗