Biology subjects

Huang, Q.

Publications and source records attributed to Huang, Q..

At least 145 records · Page 8Linked to original sources

bioRxiv2022

G6PD Inhibition Sensitizes Ovarian Cancer Cells to Oxidative Stress in the Metastatic Omental Microenvironment

Ovarian cancer (OC) is the most lethal gynecological malignancy, with aggressive metastatic disease responsible for the majority of ovarian cancer related deaths. In particular, OC tumors preferentially metastasize to and proliferate rapidly in the omentum. Here, we show metastatic OC cells experience increased oxidative stress in the omental microenvironment. Metabolic reprogramming, including upregulation of the pentose phosphate pathway (PPP), a key cellular redox homeostasis mechanism, allows OC cells to compensate for this challenge. Inhibition of G6PD, the rate-limiting enzyme of the PPP, reduces tumor burden in pre-clinical models of OC, suggesting this adaptive metabolic dependency is important for OC omental metastasis. HighlightsO_LIThe omental microenvironment poses a high oxidative stress metastatic niche for ovarian cancer cells. C_LIO_LIG6PD, a key enzyme involved in redox homeostasis and the rate-limiting enzyme of the pentose phosphate pathway (PPP) is upregulated in omental metastasis. C_LIO_LIInhibition of G6PD increases oxidative stress and cytotoxicity in the omental microenvironment. C_LIO_LIPharmacological G6PD inhibition reduces omental metastases in vivo. C_LI

cancer biology↗

bioRxiv2022

Shell Microelectrode Arrays (MEAs) for brain organoids

Brain organoids are important models for mimicking some three-dimensional (3D) cytoarchitectural and functional aspects of the brain. Multielectrode arrays (MEAs) that enable recording and stimulation of activity from electrogenic cells are widely utilized in biomedical engineering. However, conventional MEAs, initially designed for monolayer cultures, offer limited recording contact area restricted to the bottom of the 3D organoids. Inspired by the shape of electroencephalography (EEG) caps, we developed miniaturized chip-integrated MEA caps for organoids. The optically transparent shells are composed of self-folding polymer leaflets with conductive polymer-coated metal electrodes. Tunable folding of the minicaps polymer leaflets guided by mechanics simulations enables versatile recording from organoids of different sizes and we validate the feasibility of electrophysiology recording from 400-600 {micro}m sized organoids for up to four weeks and in response to glutamate stimulation. Our studies suggest that 3D shell MEAs offer significant potential for high signal-to-noise and 3D spatiotemporal brain organoid recording.

bioengineering↗

bioRxiv2022

Impact of various vaccine boosters on neutralization against Omicron following prime vaccinations with inactivated or adenovirus-vectored vaccine

Since the first report on November 24, 2021, the Omicron SARS-CoV-2 variant is now overwhelmingly spreading across the world. Two SARS-CoV-2 inactivated vaccines (IAVs), one recombinant protein subunit vaccine (PRV), and one adenovirus-vectored vaccine (AdV) have been widely administrated in many countries including China to pursue herd immunity. Here we investigated cross-neutralizing activities in 341 human serum specimens elicited by full-course vaccinations with IAV, PRV and AdV, and by various vaccine boosters following prime IAV and AdV vaccinations. We found that all types of vaccines induced significantly lower neutralizing antibody titers against the Omicron variant than against the prototype strain. For prime vaccinations with IAV and AdV, heterologous boosters with AdV and PRV, respectively, elevated serum Omicron-neutralizing activities to the highest degrees. In a mouse model, we further demonstrated that among a series of variant-derived RBD-encoding mRNA vaccine boosters, it is only the Omicron booster that significantly enhanced Omicron neutralizing antibody titers compared with the prototype booster following a prime immunization with a prototype S-encoding mRNA vaccine candidate. In summary, our systematical investigations of various vaccine boosters inform potential booster administrations in the future to combat the Omicron variant.

immunology↗

bioRxiv2022

Oxytocin modulates social brain network correlations in resting and task state

The effects of oxytocin (OT) on the social brain can be tracked upon assessing the neural activity in resting and task states, and developing a system-level framework for characterizing the state-based functional relationships of its distinct effect. Here, we contribute to this framework by examining how OT modulates social brain network correlations during resting and task states, using fMRI. First, we investigated network activation, followed by an analysis of the relationships between networks and individual differences. Subsequently, we evaluated the functional connectivity in both states. Finally, the relationship between networks across states was represented by the predictive power of networks in the resting state for task-evoked activities. The differences in the predicted accuracy between the subjects displayed individual variations in this relationship. Our results showed that the activity of the dorsal default mode network (DDMN) in the resting state had the largest predictive power for task-evoked activation of the precuneus network (PN) only in the OT group. The results also demonstrated that OT reduced the individual variation in PN in the prediction process. These findings suggest a distributed but modulatory effect of OT on the association between resting and task-dependent brain networks.

neuroscience↗

bioRxiv2021

A single-cell genomic strategy for alternative transcript start sites identification

Alternative transcription start sites (TSSs) usage plays a critical role in gene transcription regulation in mammals. However, precisely identifying alternative TSSs remains challenging at the genome-wide level. Here, we report a single-cell genomic technology for alternative TSSs annotation and cell heterogeneity detection. In the method, we utilize Fluidigm C1 system to capture individual cells of interest, SMARTer cDNA synthesis kit to recover full-length cDNAs, then dual priming oligonucleotide system to specifically enrich TSSs for genomic analysis. We apply this method to a genome-wide study of alternative TSSs identification in two different IFN-{beta} stimulated mouse embryonic fibroblasts (MEFs). We quantify the performance of our method and find it as accurate as other single cell methods for the detection of TSSs. Our data are also clearly discriminate two IFN-{beta} stimulated MEFs. Moreover, our results indicate 82% expressed genes in these two cell types containing multiple TSSs, which is much higher than previous predictions based on CAGE (58%) or empirical determination (54%) in various cell types. This indicates that alternative TSSs are more pervasive than expected and implies our strategy could position them at an unprecedented sensitivity. It would be helpful for elucidating their biological insights in future.

genomics↗

bioRxiv2021

A human monoclonal antibody potently pan-neutralizes SARS-CoV-2 VOCs by targeting RBD invariant sites

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel corona virus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.

immunology↗

bioRxiv2021

Integrative Omics Analysis Reveals the Immunomodulatory Effects of the Parasitic Dinoflagellate Hematodinium on Crustacean Immunity

Parasitic dinoflagellates in genus Hematodinium have caused substantial economic losses to multiple commercially valuable marine crustaceans around the world. In the present study, comprehensive omics approaches (miRNA transcriptomics, iTRAQ-based proteomics) were applied to investigate the host-parasite interaction between hemocytes from Portunus trituberculatus and Hematodinium perezi. The parasitic dinoflagellate remodeled the miRNome and proteome of hemocytes from challenged hosts, modulated the host immune response at both post-transcriptional and translational levels and caused post-transcriptional regulation to the host immune response. Multiple important cellular and humoral immune-related pathways (ex. Apoptosis, Endocytosis, ECM-receptor interaction, proPO activation pathway, Toll- like signaling pathway, Jak-STAT signaling pathway) were significantly affected by Hematodinium parasites. Through modulation of the host miRNome, the host immune responses of nodulation, proPO activation and antimicrobial peptides were significantly suppressed. Cellular homeostasis was imbalanced via post-transcriptional dysregulation of the phagosome, peroxisome, and lysosome pathways. Cellular structure and communication was seriously impacted by post-transcriptional downregulation of ECM-receptor interaction and focal adhesion pathways. Author summaryThe parasitic dinoflagellate Hematodinium infects many economically important marine crustaceans. Recent efforts to better understand the life cycle and biology of the parasite have improved our understanding of the disease ecology. However, studies on the host-parasite interaction, especially how Hematodinium parasites evade the host immune response are lacking. To address this shortfall, we used miRNA transcriptomics and iTRAQ-based proteomic approaches to explore the immune responses of Portunus trituberculatus when challenged with Hematodinium perezi. Striking changes in the miRNome and proteome of hemocytes were observed, and the parasite exhibited multifaceted immunomodulatory effects and potential immune-evasion mechanisms in this crustacean host.

immunology↗

bioRxiv2021

Repressing PTB is incapable to convert reactive astrocytes to dopaminergic neurons in a mouse model of Parkinson's disease

Lineage reprograming of resident glia cells to induced dopaminergic neurons (iDAns) holds attractive prospect for cell-replacement therapy of Parkinsons disease (PD). Recently, whether repressing polypyrimidine tract binding protein 1 (PTBP1) could truly achieve efficient astrocyte-to-iDAn conversion in substantia nigra and striatum aroused widespread controversy. Although reporter positive iDAns were observed by two groups after delivering adeno-associated virus (AAV) expressing a reporter with shRNA or Crispr-CasRx to repress astroglial PTBP1, the possibility of AAV leaking into endogenous DAns could not be excluded without using a reliable lineage tracing method. By adopting stringent lineage tracing strategy, two other studies showed that neither knockdown nor genetic deletion of quiescent astroglial PTBP1 fails to obtain iDAns under physiological condition. However, the role of reactive astrocyte might be underestimated since upon brain injury, reactive astrocyte could acquire certain stem cell hallmarks which may facilitate the lineage conversion process. Therefore, whether reactive astrocytes could be genuinely converted to DAns after PTBP1 repression in a PD model needs further validation. In this study, we used Aldh1l1-CreERT2-mediated specific astrocyte-lineage tracing method to investigate whether reactive astrocytes could be converted to DAns in the 6-OHDA PD model. However, we found that no astrocyte-originated DAn was generated after effective knockdown of astroglial PTBP1 either in the substantia nigra or in the striatum, while AAV "leakage" to nearby neurons was observed. Our results further confirmed that repressing PTBP1 is unable to convert astrocytes to DAns no matter in physiological or PD-related pathological conditions. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=69 SRC="FIGDIR/small/468309v2_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@fa2fa5org.highwire.dtl.DTLVardef@14e328eorg.highwire.dtl.DTLVardef@d93faborg.highwire.dtl.DTLVardef@e32225_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIAAV-shPtbp1 rapidly and efficiently induces viral-reporter-labeled DAns in mouse brain under physiological condition C_LIO_LIViral-reporter-positive DAns are not originated from PTBP1 repressed and lineage traced reactive astrocytes in a mouse PD model C_LI

neuroscience↗

bioRxiv2021

Multi-omics analysis for potential inflammation-related genes involved in tumor immune evasion via extended application of epigenetic data

BackgroundAccumulating evidence suggests that inflammation-related genes may play key roles in tumor immune evasion. Programmed cell death ligand 1 (PD-L1) is an important immune checkpoint involved in mediating antitumor immunity. We performed multi-omics analysis to explore key inflammation-related genes affecting the transcriptional regulation of PD-L1 expression. MethodsThe open chromatin region of the PD-L1 promoter was mapped using the assay for transposase-accessible chromatin using sequencing (ATAC-seq) profiles. Correlation analysis of epigenetic data (ATAC-seq) and transcriptome data (RNA-seq) were performed to identify inflammation-related transcription factors whose expression levels were correlated with the chromatin accessibility of the PD-L1 promoter. Chromatin immunoprecipitation sequencing (ChIP-seq) profiles were used to confirm the physical binding of the TF STAT2 and the predicted binding regions. We also confirmed the results of the bioinformatics analysis with cell experiments. ResultsWe identified chr9:5449463-5449962 and chr9:5450250-5450749 as reproducible open chromatin regions in the PD-L1 promoter. Moreover, we observed a correlation between STAT2 expression and the accessibility of the aforementioned regions. Furthermore, we confirmed its physical binding through ChIP-seq profiles and demonstrated the regulation of PD-L1 by STAT2 overexpression in vitro. Multiple databases were also used for the validation of the results. ConclusionOur study identified STAT2 as a direct upstream TF regulating PD-L1 expression. The interaction of STAT2 and PD-L1 might be associated with tumor immune evasion in cancers, suggesting the potential value for tumor treatment.

immunology↗

bioRxiv2021

A causality-inspired feature selection method for cancer imbalanced high-dimensional data

It is significant but challenging to explore a subset of robust biomarkers to distinguish cancer from normal samples on high-dimensional imbalanced cancer biological omics data. Although many feature selection methods addressing high dimensionality and class imbalance have been proposed, they rarely pay attention to the fact that most classes will dominate the final decision-making when the dataset is imbalanced, leading to instability when it expands downstream tasks. Because of causality invariance, causal relationship inference is considered an effective way to improve machine learning performance and stability. This paper proposes a Causality-inspired Least Angle Nonlinear Distributed (CLAND) feature selection method, consisting of two branches with a class-wised branch and a sample-wised branch representing two deconfounder strategies, respectively. We compared the performance of CLAND with other advanced feature selection methods in transcriptional data of six cancer types with different imbalance ratios. The genes selected by CLAND have superior accuracy, stability, and generalization in the downstream classification tasks, indicating potential causality for identifying cancer samples. Furthermore, these genes have also been demonstrated to play an essential role in cancer initiation and progression through reviewing the literature. Author SummarySelecting trustworthy biomarkers from high-dimensional data is an important step to help researchers and clinicians understand which genes play key roles in cancer development and progression. A large number of machine learning-based feature selection algorithms have been generated in recent years for biomarker discovery. However, these methods usually show unstable results in the face of class-imbalanced biological data, making it seem unreliable for researchers. Here we introduce the causal theory with the property of causal invariance to aid in the design of feature selection algorithms, analyze how imbalanced distributions affect feature selection methods, and propose a novel causality-based feature selection method. The method with bilateral structure adjusts the data distribution from both class-wise and sample-wise to eliminate the effect of imbalance on the results. Additionally, CLAND can simultaneously address the nonlinearity and high-dimensionality of cancer data, which broaden its application scope. We conducted extensive experiments on six real imbalance cancer datasets and obtained efficient and stable results, while the obtained biomarker has significant biological significance.

bioinformatics↗

bioRxiv2021

New Insights into the Mechanisms Used by Inhibitors Targeting Glutamine Metabolism in Cancer Cells

Many cancer cells become dependent on glutamine metabolism to compensate for glycolysis being uncoupled from the TCA cycle. The mitochondrial enzyme Glutaminase C (GAC) satisfies this glutamine addiction by catalyzing the first step in glutamine metabolism, making it an attractive drug target. Despite one of the allosteric inhibitors (CB-839) being in clinical trials, none of the drugs targeting GAC are approved for cancer treatment and their mechanism of action is not well understood. A major challenge has been the rational design of better drug candidates: standard cryo-cooled X-ray crystal structures of GAC bound to CB-839 and its analogs fail to explain their potency differences. Here, we address this problem by using an emerging technique, serial room temperature crystallography, which enabled us to observe clear differences between the binding conformations of inhibitors with significantly different potencies. A computational model was developed to further elucidate the molecular basis of inhibitor potency. We then corroborated the results from our modeling efforts by using recently established fluorescence assays that directly read-out inhibitor binding to GAC. Together, these findings provide new insights into the mechanisms used by a major class of allosteric GAC inhibitors and for the future rational design of more potent drug candidates.

biochemistry↗

bioRxiv2021

Benchmarking Computational Integration Methods for Spatial Transcriptomics Data

The increasing popularity of spatial transcriptomics has allowed researchers to analyze transcriptome data in its tissue samples spatial context. Various methods have been developed for detecting SV (spatially variable) genes, with distinct spatial expression patterns. However, the accuracy of using these SV genes in clustering has not been thoroughly studied. On the other hand, in single cell resolution sequencing data without spatial context, clustering analysis is usually done on highly variable (HV) genes. Here we investigate if integrating SV genes and HV genes from spatial transcriptomics data can improve clustering performance beyond using SV genes alone. We examined three methods that detect SV genes, including Giotto, spatialDE, and SPARK, and evaluated six methods that integrate different features measured from the same samples including MOFA+, scVI, Seurat v4, CIMLR, SNF, and the straightforward concatenation approach. We applied these methods on 19 real datasets from three different spatial transcriptomics technologies (merFISH, SeqFISH+, and Visium) as well as 20 simulated datasets of varying spatial expression conditions. Our evaluations show that MOFA+ and simple concatenation have good performances in general, despite the variations among datasets and spatial transcriptomics platforms. This work shows that integrating highly variable and spatially variable genes in the spatial transcriptomics data can improve clustering beyond using spatially variable genes only. It also provides practical guides on the choices of computational methods to accomplish this goal.

bioinformatics↗

bioRxiv2021

Air-nanobubbles ineffective to reduce pathogenic bacteria in fresh and brackish waters

Nanobubble (NB) technology has been hailed as a novel way to disinfect water. Previous studies suggested that when NBs collapse, they create shock waves that result in OH- free radicals, which can damage cells, including bacteria. In this study, we investigated, through a series of 11 experiments, the potential use of air nanobubbles (128 {+/-} 44 nm, mean {+/-} SD) to reduce the concentration of various pathogenic bacteria including Aeromonas hydrophila, A. veronii, Vibrio parahaemolyticus, and Streptococcus agalactiae under controlled, tank-based laboratory conditions. Despite the high number of nanobubbles continuously added to a relatively small volume of water in experimental tanks (50-100 L), we did not observe a consistent or significant decrease in bacteria that would control disease outbreaks. Although most of the experiments were conducted in fresh water on A. hydrophila, results were consistent across fresh and brackish water experiments, Gram-negative and Gram-positive bacteria, and a range of nanobubble concentrations. This study suggests air nanobubbles on their own are inadequate to significantly reduce high levels of pathogenic bacteria in water. We propose to explore other gases for improving the disinfection properties of this technology. SIGNIFICANCE STATEMENTAir nanobubbles did not sufficiently reduce the level of bacteria in laboratory experiments.

microbiology↗

bioRxiv2021

Extent and complexity of RNA processing in the development of honey bee queen and worker castes revealed by Nanopore direct RNA sequencing

The distinct honey bee (Apis mellifera) worker and queen castes have become a model for the study of genomic mechanisms of phenotypic plasticity. Prior studies have explored differences in gene expression and methylation during development of the two castes, but thus far no study has performed a genome-wide analysis of differences in RNA processing. To address this here we performed a Nanopore-based direct RNA sequencing with exceptionally long reads to compare the mRNA transcripts between honey bee queen and workers at three points during their larval development. We found thousands of significantly differentially expressed isoforms (DEIs) between queen and worker larvae. Most DEIs contained alternative splicing, and many of them contained at least two types of alternative splicing patterns, indicating complex RNA processing in honey bee caste differentiation. We found a negative correlation between poly(A) length and DEI expression, suggesting that poly(A) tails participate in the regulation of isoform expression. Hundreds of isoforms uniquely expressed in either queens or workers during their larval development, and isoforms were expressed at different points in queen and worker larval development demonstrating a dynamic relationship between isoform expression and developmental mechanisms. These findings show the full complexity of RNA processing and transcript expression in honey bee phenotypic plasticity.

developmental biology↗

bioRxiv2021

A dinucleotide tag-based parallel reporter gene assay method

The causal SNPs leading to increased cancer predisposition mainly function as gene regulatory elements, the evaluation of which largely rely on the parallel reporter gene assay system. However, the common DNA barcode-based parallel reporter gene assay systems are troubled with tag bias, mainly due to the tag nucleotide composition. Here we describe a versatile dinucleotide-tag reporter system (DiR) that enables parallel analysis of regulatory elements with minimized bias based on the next-generation sequencing. The DiR system is also more robust than the classical luciferase assay method, especially in the investigation of moderate-level regulatory elements. We applied DiR-seq assay in the functional evaluation of the prostate cancer risk SNPs in prostate cancer cell lines and disclosed 2, and 6 regulatory SNPs in PC-3 and LNCaP cells. The DiR system has great potential to advance the functional study of risk SNPs that have associations with polygenic diseases.

molecular biology↗

bioRxiv2021

DAB2IP inhibits p53 ubiquitin-mediated degradation by competitively binding to GRP75 and suppresses tumor malignancy in colon cancer

Increasing evidence has shown that DAB2IP acts as a tumor suppressor and plays an inhibition role in many tumors. However, the underlying mechanism is still uncertain. Our study shows that DAB2IP is positively associated with a better prognosis in colon cancer patients with wild-type TP53 expression. In vitro assay shows that DAB2IP elicits potent tumor-suppressive effects on inhibiting cell invasiveness, colony formation and promoting cell apoptosis in wild-type TP53 colon cancer cell lines. Subsequently, DAB2IP is demonstrated to up-regulate the stability of wild-type TP53 by inhibiting its degradation in a ubiquitin-proteasome-dependent manner. Using mass spectrometry profiling, we unveil that DAB2IP and p53 could both interact with the ubiquitin ligase-related protein, GRP75. Mechanistically, DAB2IP could competitively bind with GRP75, thus reducing GRP75-mediated p53 ubiquitination and degradation. Finally, animal experiments also reveal that DAB2IP inhibits the tumor progression in vivo. In conclusion, our study presents a novel function of DAB2IP in GRP75-driven wild-type p53 degradation, which provides a new insight in DAB2IP-induced tumor suppression and provides a novel molecular aspect of the p53 pathway.

cancer biology↗

bioRxiv2021

HAUSP Stabilizes SOX2 through Deubiquitination to Maintain Self-renewal and Tumorigenic Potential of Glioma Stem Cells

Glioblastoma (GBM) is the most lethal brain tumor containing glioma stem cells (GSCs) that promote malignant growth and therapeutic resistance. The self-renewal and tumorigenic potential of GSCs are maintained by core stem cell transcription factors including SOX2. Defining the posttranslational regulation of SOX2 may offer new insights into GSC biology and potential therapeutic opportunity. Here, we discover that HAUSP stabilizes SOX2 through deubiquitination to maintain GSC self-renewal and tumorigenic potential. HAUSP is preferentially expressed in GSCs in perivascular niches in GBMs. Disrupting HAUSP by shRNA or its inhibitor P22077 promoted SOX2 degradation, induced GSC differentiation, impaired GSC tumorigenic potential, and suppressed GBM tumor growth. Importantly, pharmacological inhibition of HAUSP synergized with radiation to inhibit GBM growth and extended animal survival, indicating that targeting HAUSP may overcome GSC-mediated radioresistance. Our findings reveal an unappreciated crucial role of HAUSP in the GSC maintenance and provide a promising target for developing effective anti-GSC therapeutics to improve GBM treatment. HighlightsO_LIHAUSP deubiquitinates and stabilizes SOX2 in glioma stem cells (GSCs). C_LIO_LIHAUSP is preferentially expressed by GSCs in perivascular niches in GBMs. C_LIO_LIHAUSP is required for maintaining GSC self-renewal and tumorigenic potential. C_LIO_LITargeting HAUSP inhibited malignant growth in GSC-derived GBM xenografts. C_LIO_LIInhibition of HAUSP synergized with radiation to suppress GBM tumor growth. C_LI

cancer biology↗

bioRxiv2021

Induce Pluripotency via Specific distal enhancer-promoter associations

Induced pluripotent stem cell (iPSC) technology promises to be an inexhaustible source of any type of cell needed for therapeutic and research purposes. It is unclear that how distal enhancer-promoter associations/ 3D chromatin conformation involving in the capacity of self-renewal and pluripotency maintenance. In this study, we have selected a few defined enhancer-promoter associations. After screening of enhancer specificity and activity individually, we design the different combinations and transfect these enhancers into the MEF cells. We simultaneously transfect 7 determined enhancers which represents various specific distal chromatin associations into a GFP tracing MEF cell line. We observe that the MEF cells start generating iPS-like clones at day 22. Importantly, our validations with three germ layer marker genes and in vitro experiments have further confirmed the pluripotency of these clones. Here, our study proposes a potential de novo method of a low-genetic risk iPS generation by introducing spatiotemporal distal chromatin associations. This result also paves out the way on utilizing 3D genomic information to alter cell identity and reprogramming for potential therapeutic strategy.

genomics↗