Biology subjects

Chen, Q.

Publications and source records attributed to Chen, Q..

At least 289 records · Page 16Linked to original sources

bioRxiv2022

Electron Videography of a Lipid-Protein Tango

Biological phenomena ranging from enzymatic catalysis to synaptic transmission find their origins in the morphological fluctuations of biomolecules and biomolecular assemblies in liquid water. However, directly imaging these nanoscopic dynamics without probes or labels has been a fundamental methodological challenge. Here we developed an approach for molecular videography--combining liquid-phase transmission electron microscopy with molecular modelling--with which we filmed the nanoscale morphological fluctuations of individual, freely suspended, and unlabelled membrane protein nanodiscs in liquid. These unprecedented observations enabled us to quantify fingerprints of nanoscale lipid-protein interactions directly, revealing that nanodisc shape undulations are defined by the molecular mechanics of encircling scaffold proteins, whereas lipid interactions with a membrane protein reach across surprisingly long ranges to delineate dynamically modified membrane domains and increase nanodisc stability. Overall, this work illustrates an experimental approach to image, quantify, and understand biomolecular dynamics at the nanometre scale.

biophysics↗

bioRxiv2022

Long-read genome assemblies reveals a cis-regulatory landscape associated with phenotypic divergence in two sister Siniperca fishes

BackgroundDissecting the genetic basis of variation in the regulation of gene expression is essential for understanding phenotypic evolution. Structural variants intersecting the cis-regulatory elements are found to cause gene expression variation in several developmental genes, resulting in morphological divergence between species. Due to the difficulty of identifying structural variants accurately across the genome, a comprehensive study of impacts of structural variants in cis-regulatory divergence of closely related species, especially fish species, is still scarce. Recently identified broad H3K4me3 domains are essential for the regulation of genes involved in several biological processes. However, the role of broad H3K4me3 domains in phenotypic divergence remain poorly understood. Siniperca chuatsi and S. scherzeri are two closely related fish species diverge in several phenotypic traits, making them an ideal model to study cis-regulatory evolution in closely related species. ResultsWe generated chromosome-level genomes of S. chuatsi and S. scherzeri. The evolutionary histories of S. chuatsi and S. scherzeri were studied by inferring the dynamic changes in the ancestral population sizes. The genetic basis of adaptation in S. chuatsi and S. scherzeri was dissected by performing gene family expansion and contraction analysis and identifying positively selected genes (PSGs). To investigate the role of SVs in cis-regulatory divergence of closely related fish species, we identified high-quality SVs between S. chuatsi and S. scherzeri, as well as H3K27ac and H3K4me3 domains. Integrated analysis revealed that cis-regulatory divergence caused by SVs played an essential role in the differentiation of metabolism, skin pigmentation, and immunity between S. chuatsi and S. scherzeri. Additionally, divergent broad H3K4me3 domains were found to mostly associate with cancer-related genes in S. chuatsi and S. scherzeri and contribute to their phenotypic divergence. ConclusionsOur analysis reveals SVs play an essential role in cis-regulatory variation between the two sister fish species, which in turn contributes to their phenotypic divergence. The divergence of broad H3K4me3 domains contributes to phenotypic divergence between closely related species. Additionally, the association of broad H3K4me3 domains and cancer-related genes has an ancient origin.

genomics↗

bioRxiv2022

GSK-3484862 targets DNMT1 for degradation in cells

Maintenance of genomic methylation patterns at DNA replication forks by DNMT1 is the key to faithful mitotic inheritance. DNMT1 is often overexpressed in cancer cells and the DNA hypomethylating agents azacytidine and decitabine are currently used in the treatment of hematologic malignancies. However, the toxicity of these cytidine analogs and their ineffectiveness in treating solid tumors have limited wider clinical use. GSK-3484862 is a newly-developed, dicyanopyridine containing, non-nucleoside DNMT1-selective inhibitor with low cellular toxicity. Here, we show that GSK-3484862 targets DNMT1 for protein degradation in both cancer cell lines and murine embryonic stem cells (mESCs). DNMT1 depletion was rapid, taking effect within hours following GSK-3484862 treatment, leading to global hypomethylation. Inhibitor-induced DNMT1 degradation was proteasome-dependent, with no discernible loss of DNMT1 mRNA. In mESCs, GSK-3484862-induced Dnmt1 degradation requires Uhrf1, an accessory factor of Dnmt1 with E3 ubiquitin ligase activity. We also show that Dnmt1 depletion and DNA hypomethylation induced by the compound are reversible after its removal. Together, these results indicate that this DNMT1-selective degrader/inhibitor will be a valuable tool for dissecting both coordinated events linking DNA methylation to gene expression and identifying downstream effectors that ultimately regulate cellular response to altered DNA methylation patterns in a tissue/cell-specific manner. HighlightsO_LIGSK-3484862 targets DNMT1 for protein degradation in a wide-range of cancer cell lines, without a decrease in DNMT1 mRNA levels C_LIO_LIDNMT1 depletion leads to a >50% loss of global DNA methylation in cells within 2-days of treatment with GSK-3484862 C_LIO_LIGSK-3484862-induced DNMT1 degradation is proteasome-dependent C_LIO_LIIn mESCs, Uhrf1 is required for GSK-3484862 to induce Dnmt1 degradation C_LI

cancer biology↗

bioRxiv2022

Quartet metabolite reference materials for assessing inter-laboratory reliability and data integration of metabolomic profiling

Various laboratory-developed metabolomic methods lead to big challenges in inter-laboratory comparability and effective integration of diverse datasets. As part of the Quartet Project, we established a publicly available suite of four metabolite reference materials derived from B-lymphoblastoid cell lines from a family quartet of parents and monozygotic twin daughters. We generated comprehensive LC-MS based metabolomic data from the Quartet reference materials using targeted and untargeted strategies in different laboratories. High variabilities in the qualitative and quantitative metabolomic measurements were observed across laboratories. Moreover, the Quartet multi-sample-based quality metrics were developed for objectively assessing the reliability of metabolomic profiling in detecting intrinsic biological differences among difference groups of samples. Importantly, the ratio-based metabolomic profiling, by scaling the absolute values of a study sample relative to those of a universal reference sample, enables data integration in long-term measurements across difference laboratories or platforms. Thus, we constructed the ratio-based high-confidence reference datasets between two reference samples, providing "ground truth" for inter-laboratory proficiency test, which enables objective assessment of various metabolomic methods. Our study provided the community with rich resources and best practice for objective assessment of inter-laboratory measurements and data integration, ensuring reliable large-scale and longitudinal metabolomic profiling.

systems biology↗

bioRxiv2022

(Z, Z, Z)-3,6,9-nonadecadiene, a potential inhibitor of sex pheromone of Ectropis grisescens Warren (Lepidoptera: Geometridae): electroantennogram test, wind tunnel, and in silico study

Application of sex pheromone is the most environmental-friendly technique to control pests. Moreover, it has been discovered that pheromone analogs can disturb or inhibit mating communication in some species of moths. Ectropis grisescens Warren (Lepidoptera: Geometridae), is the most severe tea defoliator in China. Thus, in our study, an analog of the pest sex pheromone component, (Z, Z, Z)-3,6,9-nonadecadiene (Z3Z6Z9-19:Hy), was selected to determine its potential activity in controlling the pest. Electroantennogram (EAG), Y-tube olfactometer, and wind tunnel experiments separately showed potential inhibition of Z3Z6Z9-19:Hy. The response elicited by Z3Z6Z9-19:Hy displayed a dose-dependent way in EAG test. Furthermore, in Y-tube olfactometer, percentage of positive response of E. grisescens males was significantly (P<0.01) reduced by Z3Z6Z9-19:Hy up to 70%. In wind tunnel, all types of behavioral response were significantly (P<0.01) inhibited by Z3Z6Z9-19:Hy, percentage of contacting source was utterly inhibited at the lowest dose tested. Based on these results, the combination of the analog and SNMP1 protein was also studied. Our study revealed the potential of Z3Z6Z9-19:Hy as a sex pheromone inhibitor, which would provide new perspectives in monitoring and mating disruption of E. grisescens in pest-control strategies.

ecology↗

bioRxiv2022

Ratio-based quantitative multiomics profiling using universal reference materials empowers data integration

Multiomics profiling is a powerful tool to characterize the same samples with complementary features orchestrating the genome, epigenome, transcriptome, proteome, and metabolome. However, the lack of ground truth hampers the objective assessment of and subsequent choice from a plethora of measurement and computational methods aiming to integrate diverse and often enigmatically incomparable omics datasets. Here we establish and characterize the first suites of publicly available multiomics reference materials of matched DNA, RNA, proteins, and metabolites derived from immortalized cell lines from a family quartet of parents and monozygotic twin daughters, providing built-in truth defined by family relationship and the central dogma. We demonstrate that the "ratio"-based omics profiling data, i.e., by scaling the absolute feature values of a study sample relative to those of a concurrently measured universal reference sample, were inherently much more reproducible and comparable across batches, labs, platforms, and omics types, thus empower the horizontal (within-omics) and vertical (cross-omics) data integration in multiomics studies. Our study identifies "absolute" feature quantitation as the root cause of irreproducibility in multiomics measurement and data integration, and urges a paradigm shift from "absolute" to "ratio"-based multiomics profiling with universal reference materials.

systems biology↗

bioRxiv2022

Correcting batch effects in large-scale multiomic studies using a reference-material-based ratio method

Batch effects are notorious technical variations that are common in multiomic data and may result in misleading outcomes. With the era of big data, tackling batch effects in multiomic integration is urgently needed. As part of the Quartet Project for quality control and data integration of multiomic profiling, we comprehensively assess the performances of seven batch-effect correction algorithms (BECAs) for mitigating the negative impact of batch effects in multiomic datasets, including transcriptomics, proteomics, and metabolomics. Performances are evaluated based on accuracy of identifying differentially expressed features, robustness of predictive models, and the ability of accurately clustering cross-batch samples into their biological sample groups. Ratio-based method is more effective and widely applicable than others, especially in cases when batch effects are highly confounded with biological factors of interests. We further provide practical guidelines for the implementation of ratio-based method using universal reference materials profiled with study samples. Our findings show the promise for eliminating batch effects and enhancing data integration in increasingly large-scale, cross-batch multiomic studies.

systems biology↗

bioRxiv2022

Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes.

SARS-CoV-2 spike protein (S) is structurally dynamic and has been observed by cryo-EM to adopt a variety of prefusion conformations that can be categorized as locked, closed and open. The locked conformations feature tightly packed trimers with structural elements incompatible with RBD in "up" position. For SARS-CoV-2 S, it has been shown that the locked conformations are transient under neutral pH. Probably due to their transience, locked conformations remain largely uncharacterized for SARS-CoV-1 S. Intriguingly, locked conformations were the only conformations captured for S proteins of bat and pangolin origin SARS-related coronaviruses. In this study, we introduced x1, x2, and x3 disulfides into SARS-CoV-1 S. Some of these disulfides have been shown to preserve rare locked conformations when introduced to SARS-CoV-2 S. Introduction of these disulfides allowed us to image a variety of locked and other rare conformations for SARS-CoV-1 S by cryo-EM. We identified bound cofactors and structural features that are associated with SARS-CoV-1 S locked conformations. We compare newly determined structures to other available spike structures of Sarbecoviruses to identify conserved features and discuss their possible functions.

biochemistry↗

bioRxiv2022

Phylogenomics reveals the relationships of butterflies and moths (Lepidoptera): providing the potential landscape using universal single copy orthologues

BackgroundA robust and stable phylogenetic framework is a fundamental goal of evolutionary biology. As the third largest insect order following by Diptera and Coleoptera in the world, lepidoptera (butterflies and moths) play a central role in almost every terrestrial ecosystem as the indicators of environmental change and serve as important models for biologists exploring questions related to ecology and evolutionary biology. However, for such charismatic insect group, the higher-level phylogenetic relationships among its superfamilies are still poorly unresolved. Resultswe increased taxon sampling among Lepidoptera (40 superfamilies and 76 families contained 286 taxa) and filtered the unqualified samples, then acquired a series of large amino-acid datasets from 69,680 to 400,330 for phylogenomic reconstructions. Using these datasets, we explored the effect of different taxon sampling on tree topology by considering a series of systematic errors using ML and BI methods. Moreover, we also tested the effectiveness in topology robustness among the three ML-based models. The results showed that taxon sampling is an important determinant in tree robustness of accurate lepidopteran phylogenetic estimation. Long-branch attraction (LBA) caused by site-wise heterogeneity is a significant source of bias given rise to topologies divergence of ditrysia in phylogenomic reconstruction. Phylogenetic inference showed a most comprehensive framework by far to reveal the relationships among lepidopteran superfamilies, but limited by taxon sampling, it could only represent the current understanding of the lepidopteran tree of life. The relationships within the species-rich and relatively rapid radiation Ditrysia and especially Apoditrysia remain poorly unresolved, which need to increase taxon sampling and adopt lineage-specific genes for further phylogenomic reconstruction. ConclusionsThe present study further expands the taxon sampling of lepidopteran phylogeny and provides a potential phylogenomic foundation for further understanding its current higher-level relationships.

evolutionary biology↗

bioRxiv2022

Highly synchronized cortical circuit dynamics mediate spontaneous pain

Cortical neural dynamics mediate information processing for the cerebral cortex, implicated in fundamental biological processes, such as vision and olfaction, in addition to neurological and psychiatric diseases. Spontaneous pain is a key feature of human neuropathic pain. Whether spontaneous pain pushes cortical network into an aberrant state, and if so, whether it can be brought back to a normal operating range to ameliorate pain are unknown. Using a clinically relevant mouse model of neuropathic pain with robust spontaneous pain-like behavior, we report that orofacial spontaneous pain activated a specific area within the primary somatosensory cortex (S1), displaying synchronized neural dynamics revealed by intravital two-photon calcium imaging. This synchronization was underpinned by local GABAergic interneuron hypoactivity. Pain-induced cortical synchronization could be attenuated by manipulating local S1 networks or clinically effective pain therapies. Specifically, both chemogenetic inhibition of pain-related c-Fos-expressing neurons, and selective activation of GABAergic interneurons, significantly attenuated S1 synchronization. Clinically effective pain therapies including carbamazepine and nerve root decompression could also dampen S1 synchronization. More importantly, restoring a normal range of neural dynamics, through attenuating pain-induced S1 synchronization, alleviated pain-like behavior. These results suggest spontaneous pain pushes S1 regional network into a synchronized state, whereas reversal of this synchronization alleviates pain.

neuroscience↗

bioRxiv2022

Effects of antennal segments defects on blood-sucking behavior in Aedes albopictus

After mating, female mosquitoes need a blood meal to promote the reproductive process. The blood-feeding transmits extremely harmful infections including malaria, yellow fever, dengue fever, and other arboviruses, making mosquitoes one of the most harmful creatures to human health. The selection and localization of the host by mosquitoes mainly depends on the trace chemical cues emitted by the host into the environment, and the sense of smell is the main way to perceive these trace chemical cues. However, the knowledge of the olfactory mechanism is not enough to meet the needs of mosquito control. Unlike previous studies that focused on the olfactory receptor recognition spectrum to reveal the olfactory mechanism of mosquito host localization. In this paper, we proposed that artificial defects in mosquito antennal flagellomeres may affect their blood-feeding behavior, and through rationally designed behavioral experiments, we found that the 6th and 7th flagellomeres on Aedes albopictus antenna are important in the olfactory detection of host searching. Meanwhile, the morphology and distribution of sensilla on each antenna flagellomere were also analyzed and discussed in this paper.

animal behavior and cognition↗

bioRxiv2022

The Quartet Data Portal: integration of community-wide resources for multiomics quality control

The implementation of quality control for multiomic data requires the widespread use of well-characterized reference materials, reference datasets, and related resources. The Quartet Data Portal was built to facilitate community access to such rich resources established in the Quartet Project. A convenient platform is provided for users to request the DNA, RNA, protein, and metabolite reference materials, as well as multi-level datasets generated across omics, platforms, labs, protocols, and batches. Interactive visualization tools are offered to assist users to gain a quick understanding of the reference datasets. Crucially, the Quartet Data Portal continuously collects, evaluates, and integrates the community-generated data of the distributed Quartet multiomic reference materials. In addition, the portal provides analysis pipelines to assess the quality of user-submitted multiomic data. Furthermore, the reference datasets, performance metrics, and analysis pipelines will be improved through periodic review and integration of multiomic data submitted by the community. Effective integration of the evolving technologies via active interactions with the community will help ensure the reliability of multiomics-based biological discoveries. The Quartet Data Portal is accessible at https://chinese-quartet.org. Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

systems biology↗

bioRxiv2022

Quartet RNA reference materials and ratio-based reference datasets for reliable transcriptomic profiling

As an indispensable tool for transcriptome-wide analysis of differential gene expression, RNA sequencing (RNAseq) has demonstrated great potential in clinical applications. However, the lack of multi-group RNA reference materials of biological relevance and the corresponding reference datasets for assessing the reliability of RNAseq hampers its wide clinical applications wherein the underlying biological differences among study groups are often small. As part of the Quartet Project for quality control and data integration of multiomic profiling, we established four RNA reference materials derived from immortalized B-lymphoblastoid cell lines from four members of a monozygotic twin family. Additionally, we constructed ratio-based transcriptome-wide reference datasets using multi-batch RNAseq datasets, providing "ground truth" for benchmarking. Moreover, Quartet-sample-based quality metrics were developed for assessing reliability of RNAseq technology in terms of intra-batch proficiency and cross-batch reproducibility. The small intrinsic biological differences among the Quartet samples enable sensitive assessment of performance of transcriptomic measurements. The Quartet RNA reference materials combined with the reference datasets can be served as unique resources for assessing data quality and improving reliability of transcriptomic profiling.

genetics↗

bioRxiv2022

Nutrient addition increases grassland resistance during dry and wet climate extremes despite functional diversity loss

O_LINutrient enrichment impacts grassland plant diversity such as species richness, functional trait composition and diversity, but whether and how these changes affect ecosystem stability in the face of increasing climate extremes remains largely unknown. C_LIO_LIWe quantified the direct and diversity-mediated effects of nutrient addition (by nitrogen, phosphorus, and potassium) on the stability of aboveground biomass production in 10 long-term grassland experimental sites. We measured five facets of stability as the temporal invariability, resistance during and recovery after extreme dry and wet growing seasons. C_LIO_LILeaf traits (leaf carbon, nitrogen, phosphorus, potassium, and specific leaf area) were measured under ambient and nutrient addition conditions in the field and were used to construct the leaf economic spectrum (LES). We calculated functional trait composition and diversity of LES and of single leaf traits. We quantified the contribution of intraspecific trait shifts and species replacement to change in functional trait composition as responses to nutrient addition and its implications for ecosystem stability. C_LIO_LINutrient addition decreased functional trait diversity and drove grassland communities to the faster end of the LES primarily through intraspecific trait shifts, suggesting that intraspecific trait shifts should be included for accurately predicting ecosystem stability. Moreover, the change in functional trait diversity of the LES in turn influenced different facets of stability. That said, these diversity-mediated effects were overall weak and/or overwhelmed by the direct effects of nutrient addition on stability. As a result, nutrient addition did not strongly impact any of the stability facets. These results were generally consistent using individual leaf traits but the dominant pathways differed. Importantly, major influencing pathways differed using average trait values extracted from global trait databases (e.g. TRY). C_LIO_LISynthesis. Investigating changes in multiple facets of plant diversity and their impacts on multidimensional stability under global changes such as nutrient enrichment can improve our understanding of the processes and mechanisms maintaining ecosystem stability. C_LI

ecology↗

bioRxiv2022

A novel batokine Breg controls adipose thermogenesis and glucose homeostasis

Batokines selectively expressed in brown and beige adipocytes remain to be identified and their potential signaling role in adipose thermogenesis are largely unknown. Here we identified a batokine we named as Breg acting as a key regulator for adipose thermogenesis and glucose homeostasis. Breg expression is adipose-specific and highly brown fat-enriched, and its secretion is stimulated by {beta}3-adrenergic activation. Gain-of-functional studies collectively showed that secreted Breg promotes adipose thermogenesis, lowers glucose level, and protects against obesity. Adipose-specific Breg knockout mice are defective in white fat browning, and are susceptible to high fat diet-induced obesity and hyperglycemia, demonstrating the physiological importance of this batokine in energy metabolism. Mechanistically, Breg binds to a putative receptor on adipocyte surface and activates protein kinase A independently of {beta}-adrenergic signaling. These results establish Breg as a major upstream signaling component in thermogenesis and offer a potential avenue for the treatment of obesity and diabetes.

cell biology↗

bioRxiv2022

IL-12/18/21 pre-activation enhances the anti-tumor efficacy of expanded γδT cells and overcomes resistance to anti-PD-L1 treatment

{gamma}{delta}T cells are promising candidates for cellular immunotherapy due to their immune regulation through cytokine production and MHC-independent direct cytotoxicity against a broad spectrum of tumors. However, current {gamma}{delta}T cell-based cancer immunotherapy has limited efficacies and novel strategies are needed to improve its clinical outcomes. Here, we report that cytokine pre-treatment with IL-12/18, IL-12/15/18, IL-12/18/21 and IL-12/15/18/21 could effectively enhance the activation and cytotoxicity of in vitro expanded murine and human {gamma}{delta}T cells. However, only adoptive transfer of IL-12/18/21 pre-activated {gamma}{delta}T cells significantly inhibited tumor growth in a murine melanoma model and a hepatocellular carcinoma model. Both IL-12/18/21 pre-activated antibody-expanded and zoledronate-expanded human {gamma}{delta}T cells effectively controlled tumor growth in a humanized mouse model. IL-12/18/21 pre-activation promoted {gamma}{delta}T cell proliferation and cytokine production in vivo and enhanced IFN-{gamma} and TNF- production, as well as granzyme B expression by endogenous CD8+ T cells in a cell-cell contact dependent manner. Furthermore, the adoptive transfer of IL-12/18/21 pre-activated {gamma}{delta}T cells could overcome the resistance to anti-PD-L1 therapy, and the combination therapy had a synergistic effect on the therapeutic outcomes. Moreover, the enhanced anti-tumor function of adoptively transferred IL-12/18/21 pre-activated {gamma}{delta}T cells was largely diminished in the absent of endogenous CD8+T cells when administered alone or in combination with anti-PD-L1, suggesting a CD8+T cell-dependent mechanism. Taken together, IL-12/18/21 pre-activation could promote {gamma}{delta}T cell anti-tumor function and overcome the resistance to checkpoint blockade therapy, indicating an effective combinational cancer immunotherapeutic strategy. SynopsisO_LIIL-12/18/21 pre-activation enhances the anti-tumor efficacy of adoptively transferred {gamma}{delta}T cells by promoting its proliferation, activation, and cytotoxicity, as well as activating endogenous CD8+ T cells. C_LIO_LIAdoptive transfer of IL-12/18/21 pre-activated {gamma}{delta}T cells could overcome the resistance to anti-PD-L1 therapy, indicating an effective combinational cancer immunotherapeutic strategy. C_LI

immunology↗

bioRxiv2022

Cytoplasmic tail of the putative polycystin channel Pkd2 regulates its clustering in the fission yeast eisosomes

Polycystins are a family of conserved ion channels, mutations of which lead to human genetic disorder Autosomal Dominant Polycystic Kidney Disease. The unicellular model organism fission yeast Schizosacchromyces pombe possesses single essential polycystin Pkd2 that localizes to the plasma membrane and is required for cell proliferation. Here, we carried out a functional analysis of Pkd2 based on its Alphafold predicted structure. It consisted of N-terminal lipid-binding (LBD), central transmembrane (TMD) and C-terminal cytoplasmic (CCD) domains. LBD assumes a unique immunoglobulin-fold, while TMD contains nine transmembrane helices. Both were essential. Although the mostly disordered CCD was not, its removal led to clustering of Pkd2 in eisosomes, a microdomain of the plasma membrane. Inhibiting eisosome assembly prevented the clustering but disrupting ER-PM contacts further increased it. Pkd2 shared similar structure with two other putative channels Trp663 and Trp1322, but their intracellular localization and function diverged from each other. Replacing LBD with that of Trp663 partially restored the function of Pkd2, but TMD could not be replaced by either that of Trp663 or human polycystins. We concluded that both the plasma membrane microdomains and cytoplasmic tail of Pkd2 regulate the cell surface clustering of this putative ion channel.

cell biology↗

bioRxiv2022

Crossmodal reorganization in deaf auditory cortices compensates for the impaired body-centered visuomotor transformation after early deafness

Early deafness leads to the reorganization of large-scale brain networks, involving and extending beyond the auditory system. Body-centered visuomotor transformation is impaired after early auditory deprivation, associated with a hyper-crosstalk between the task-critical frontoparietal network (FPN) and the default-mode network (DMN). It remains to be elucidated, how the reorganized functional connectivity between the auditory system, the FPN, and the DMN contributes to the impaired visuomotor transformation after early deafness. In this fMRI study, we asked early deaf participants and hearing controls to judge the spatial location of a visual target, either about the middle-sagittal line of their own body (the egocentric task) or another background object (the allocentric task). The bilateral superior temporal gyrus (STG) in the deaf group exhibited cross-modal reorganization, with generally enhanced neural activity during the visual tasks, compared to hearing controls. Moreover, the STG showed significantly increased functional connectivity with both the FPN and the DMN in the deaf group compared to hearing controls, specifically during the egocentric task. The increased STG-FPN and STG-DMN coupling, however, showed antagonistic effects on the egocentric performance of the deaf participants. The increased STG-FPN connectivity was associated with improved (i.e., a beneficial role) while the increased STG-DMN with deteriorated (i.e., a detrimental role) egocentric performance in the deaf participants. No such effect was observed in hearing controls. Therefore, the auditory cortex is reorganized to functionally resemble the FPN in the deaf brain, representing compensatory neuroplasticity to mitigate the impaired visuomotor transformation after early deafness. Significance StatementOur brain constantly plans vision-guided actions, transforming visuospatial representations of external visual targets into visuomotor representations. The frontoparietal network (FPN) critically supports this visuomotor transformation process, which is impaired after early deafness. To mitigate the impaired visuomotor transformation, the deaf auditory cortex in the bilateral superior temporal gyrus (STG) shows compensatory cross-modal reorganization that functionally resembles the FPN regions. Specifically, the deaf auditory cortex becomes functionally coupled with the dorsal FPN regions. The stronger the STG-FPN coupling, the more improved the deaf adults visuomotor transformation performance, indicating the reorganized STG as a critical node of the task-critical network. Correspondingly, increased coupling between the task-critical deaf STG and the default-mode network impairs the visuomotor transformation.

neuroscience↗