Biology subjects

Zhong, S.

Publications and source records attributed to Zhong, S..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Inhibition of the transcription factor PU.1 suppresses tumor growth in mice by promoting the recruitment of cytotoxic lymphocytes through the CXCL9-CXCR3 axis

Tumor-associated macrophages (TAMs) are among the most abundant immune cells associated with tumors, which often exhibit immune regulatory phenotypes that promote tumor growth and confer resistance to anti-tumor immune therapies. Despite extensive efforts in developing immunotherapeutic strategies aimed at controlling the recruitment or reprogramming of TAMs, success has been limited due to strategic caveats, underscoring the need for a novel approach targeting the TAMs. PU.1, a lineage-dependent transcription factor, is highly expressed throughout the lifespan of macrophages. We have found that inhibition of PU.1 by the small molecule DB2313 suppresses melanoma tumor growth in mice through enhanced tumor recruitment of CD4+ T helper cells and cytotoxic T/NK cells mediated by TAMs. Whole transcriptome and targeted gene expression analyses revealed that DB2313 upregulates CXCL9 expression in bone marrow-derived macrophages (BMDMs) and TAMs. The anti-tumor effects of DB2313 were abolished by depleting macrophages with clodronate or inhibiting the CXCL9-CXCR3 chemokine axis using neutralizing antibodies against CXCL9 or CXCR3. Collectively, these results suggest that pharmacological inhibition of PU.1 suppresses tumor growth by promoting tumor infiltrating lymphocytes through the CXCL9-CXCR3 chemokine axis. Our study establishes a framework for developing TAM-modulating immunotherapies by targeting the transcriptional factor PU.1.

immunology↗

bioRxiv2024

Genome-wide identification of stable RNA-chromatin interactions

RNA-chromatin interactions play crucial roles in gene regulation and genome organization, but the interaction landscape remains poorly understood. In this study, we conducted an in-depth analysis of a previously published dataset on RNase-treated in situ mapping of the RNA-genome interactome in human embryonic stem cells. This dataset globally profiles RNase-insensitive RNA-chromatin interactions. Our analysis revealed that RNase treatment selectively preserved long-range RNA-chromatin interactions while removing promiscuous interactions resulting from the local diffusion of nascent transcripts. RNase-insensitive chromatin-associated RNAs (RI-caRNAs) exhibited high sequence conservation and preferentially localized to functional genomic regions, including promoters, transcription factor binding sites, and regions with specific histone modifications. Interestingly, coding and non-coding RNA transcripts showed distinct sensitivities to RNase, with lncRNAs and disease-associated transcripts being enriched among RI-caRNAs. Furthermore, we identified specific caRNA classes associated with individual transcription factors and histone modifications. Altogether, our findings reveal a RNase-inaccessible regulatory RNA-chromatin interactome and provide a resource for understanding RNA-mediated chromatin regulation.

genomics↗

bioRxiv2024

Genome-Wide Mapping of RNA-Protein Associations via Sequencing

RNA-protein interactions are crucial for regulating gene expression and cellular functions, with their dysregulation potentially impacting disease progression. Systematically mapping these interactions is resource-intensive due to the vast number of potential RNA and protein interactions. Here, we introduce PRIM-seq (Protein-RNA Interaction Mapping by sequencing), a method for the concurrent de novo identification of RNA-binding proteins (RBPs) and the elucidation of their associated RNAs. PRIM-seq works by converting each RNA-protein pair into a unique chimeric DNA sequence, which is then decoded through DNA sequencing. Applied to two human cell types, PRIM-seq generated a comprehensive human RNA-protein association network (HuRPA), consisting of more than 350,000 RNA-proteins pairs involving approximately 7,000 RNAs and 11,000 proteins. The data revealed an enrichment of previously reported RBPs and RNA-protein interactions within HuRPA. We also identified LINC00339 as a protein-associating non-coding RNA and PHGDH as an RNA-associating protein. Notably, PHGDH interacts with BECN1 and ATF4 mRNAs, suppressing their protein expression and consequently inhibiting autophagy, apoptosis, and neurite outgrowth while promoting cell proliferation. PRIM-seq offers a powerful tool for discovering RBPs and RNA-protein associations, contributing to more comprehensive functional genome annotations.

molecular biology↗

bioRxiv2024

Reciprocal regulation of m6A modification and miRNA production machineries via phase separation-dependent and -independent mechanisms

Methyltransferase complex (MTC) deposits N6-adenosine (m6A) onto RNA, whereas microprocessor produces miRNA. Whether and how these two distinct complexes cross-regulate each other has been poorly studied. Here we report that the MTC subunit B (MTB) tends to form insoluble condensates with poor activity, with its level monitored by 20S proteasome. Conversely, the microprocessor component SERRATE (SE) forms liquid-like condensates, which in turn promotes solubility and stability of MTB, leading to increased MTC activity. Consistently, the hypomorphic lines expressing SE variants, defective in MTC interaction or liquid-like phase behavior, exhibit reduced m6A level. Reciprocally, MTC can recruit microprocessor to MIRNA loci, prompting co-transcriptional cleavage of primary miRNA (pri-miRNAs) substrates. Additionally, pri-miRNAs carrying m6A modifications at their single-stranded basal regions are enriched by m6A readers, which retain microprocessor in the nucleoplasm for continuing processing. This reveals an unappreciated mechanism of phase separation in RNA modification and processing through MTC and microprocessor coordination.

plant biology↗

bioRxiv2024

Translatome analysis reveals cellular network in DLK-dependent hippocampal glutamatergic neuron degeneration

The conserved MAP3K12/Dual Leucine Zipper Kinase (DLK) plays versatile roles in neuronal development, axon injury and stress responses, and neurodegeneration, depending on cell-type and cellular contexts. Emerging evidence implicates abnormal DLK signaling in several neurodegenerative diseases. However, our understanding of the DLK-dependent gene network in the central nervous system remains limited. Here, we investigated the roles of DLK in hippocampal glutamatergic neurons using conditional knockout and induced overexpression mice. We found that dorsal CA1 and dentate gyrus neurons are vulnerable to elevated expression of DLK, while CA3 neurons appear less vulnerable. We identified the DLK-dependent translatome that includes conserved molecular signatures and displays cell-type specificity. Increasing DLK signaling is associated with disruptions to microtubules, potentially involving STMN4. Additionally, primary cultured hippocampal neurons expressing different levels of DLK show altered neurite outgrowth, axon specification, and synapse formation. The identification of translational targets of DLK in hippocampal glutamatergic neurons has relevance to our understanding of selective neuron vulnerability under stress and pathological conditions.

neuroscience↗

bioRxiv2024

Hemispheric multi-dimension features extraction analysis based on decoupled representation learning

The predominant approach in investigating brain structural asymmetry relies on predefined regions of interest, assessing variations between homologous brain regions through a single indicator, which is local, univariate, and relative. In response to this challenge, we employ decoupled representation learning from deep learning to extract hidden features containing hemisphere-specific information at a hemispheric systemic level. This novel approach enables a global and multivariate analysis of brain structural asymmetry. Our findings indicate a significant association between left-hemisphere-specific hidden features and language-related behavioral metrics, as well as a correlation between right-hemisphere-specific hidden features and social-related behavioral metrics. Tensor-based Morphometry results find the impact of left-hemisphere-specific features on the left inferior frontal sulcus within Brocas area, a crucial region for language processing. Additionally, right-hemisphere-specific features influenced the right rostral hippocampus, a region implicated in emotion regulation and spatial navigation. The findings from Neurosynth indicate that significant regions caused by left-hemisphere-specific features are correlated with language, while significant regions caused by right-hemisphere-specific features are associated with behaviors primarily governed by the right hemisphere. Furthermore, our study establishes a link between structural changes induced by hemisphere-specific features and several genes. Such findings demonstrate that the application of deep learning techniques allows for precise capture of hemisphere-specific information within individual hemispheres, offering a new perspective for future research on brain structural asymmetry.

neuroscience↗

bioRxiv2024

High impact AMPAkines induce a Gq-protein coupled endoplasmic calcium release in cortical neurons: a possible mechanism for explaining the toxicity of high impact AMPAkines

Positive allosteric modulators of the AMPA receptor (AMPAkines) have a multitude of promising therapeutic properties. The pharmaceutical development of high impact AMPAkines has however been limited by the appearance of calcium-dependent neuronal toxicity and convulsions in vivo. Such toxicity is not observed at exceptionally high concentrations of low impact ampakines. Since most AMPAR are somewhat impermeable to calcium, the current study sought to examine the extent to which different mechanisms contribute to the rise in intracellular calcium in the presence of high impact ampakines. In the presence of AMPA alone, cytosolic calcium elevation is shown to be sodium-dependent. In the presence of high impact AMPAkines such as cyclothiazide (CTZ) or CX614, however, AMPAR potentiation also activates an additional mechanism that induces calcium release from endoplasmic reticular (ER) stores. The pathway that connects AMPAR to the ER system involves a Gq-protein, phospholipase C{beta}-mediated inositol triphosphate (InsP3) formation and ultimately stimulation of InsP3-receptors located on the ER. The same linkage was not observed using high concentrations of the low impact AMPAkines, CX516 (Ampalex) and CX717. We also demonstrate that CX614 produces neuronal hyper-excitability at therapeutic doses while the newer generation low impact AMPAkine CX1739 is safe at exceedingly high doses. While earlier studies have demonstrated a functional linkage between AMPAR and G-proteins, this report demonstrates that in the presence of high impact AMPAkines, AMPAR also couple to a Gq-protein, which triggers a secondary calcium release from the ER and provides insight into the disparate actions of high and low impact AMPAkines.

pharmacology and toxicology↗

bioRxiv2024

Turnover of RNA-binding Proteins and MicroRNAs by intrinsically disordered region-directed ZSWIM8 ubiquitin ligase during brain development

Widely present in mammalian proteomes, intrinsically disordered regions (IDRs) in proteins play important biological functions by conferring structural flexibility and mediating biomolecular interactions. IDR-containing proteins, including many RNA-binding proteins (RBPs), are prone to misfolding and aggregation and must be constantly monitored. Here we show that the conserved ZSWIM8-type Cullin-RING ubiquitin ligase (CRLZSWIM8) is a master regulator of such proteins during brain development. ZSWIM8 selects its substrates via an IDR-dependent mechanism, and deletion of ZSWIM8 causes aberrant accumulation of numerous RBPs including AGO2 and ELAV1 in neonatal brains. Furthermore, AGO2 ubiquitination by ZSWIM8 is triggered by microRNA binding, leading to target-directed microRNA degradation (TDMD) of MiR7. Dysregulation of MiR7 in the absence of ZSWIM8 results in defects in oligodendrocyte maturation and functions. Together, our findings have demonstrated that, by utilizing variable target-recognition strategies, ZSWIM8 controls the abundance of conformationally flexible RBPs and miRNA metabolism that are essential for brain development. TeaserA conserved ubiquitin ligase controls the quality of disordered proteins to ensure brain development.

developmental biology↗

bioRxiv2024

Evolution of cell-type-specific accessible chromatin regions and the cis-regulatory elements that drive lineage-specific innovation

Cis-regulatory elements (CREs) are critical in regulating gene expression, and yet understanding of CRE evolution remains challenging. Here, we constructed a comprehensive single-cell atlas of chromatin accessibility in Oryza sativa, integrating data from 103,911 nuclei representing 126 discrete cell states across nine distinct organs. We used comparative genomics to compare cell-type resolved chromatin accessibility between O. sativa and 57,552 nuclei from four additional grass species (Zea mays, Sorghum bicolor, Panicum miliaceum, and Urochloa fusca). Accessible chromatin regions (ACRs) had different levels of conservation depending on the degree of cell-type specificity. We found a complex relationship between ACRs with conserved noncoding sequences, cell-type specificity, conservation, and tissue-specific switching. Additionally, we found that epidermal ACRs were less conserved compared to other cell types, potentially indicating that more rapid regulatory evolution has occurred in the L1-derived epidermal layer of these species. Finally, we identified and characterized a conserved subset of ACRs that overlapped the repressive histone modification H3K27me3, implicating them as potentially silencer-like CREs maintained by evolution. Collectively, this comparative genomics approach highlights the dynamics of plant cell-type-specific CRE evolution.

plant biology↗

bioRxiv2024

Investigating the cis-Regulatory Basis of C3 and C4 Photosynthesis in Grasses at Single-Cell Resolution

While considerable knowledge exists about the enzymes pivotal for C4 photosynthesis, much less is known about the cis-regulation important for specifying their expression in distinct cell types. Here, we use single-cell-indexed ATAC-seq to identify cell-type-specific accessible chromatin regions (ACRs) associated with C4 enzymes for five different grass species. This study spans four C4 species, covering three distinct photosynthetic subtypes: Zea mays and Sorghum bicolor (NADP-ME), Panicum miliaceum (NAD-ME), Urochloa fusca (PEPCK), along with the C3 outgroup Oryza sativa. We studied the cis-regulatory landscape of enzymes essential across all C4 species and those unique to C4 subtypes, measuring cell-type-specific biases for C4 enzymes using chromatin accessibility data. Integrating these data with phylogenetics revealed diverse co-option of gene family members between species, showcasing the various paths of C4 evolution. Besides promoter proximal ACRs, we found that, on average, C4 genes have two to three distal cell-type-specific ACRs, highlighting the complexity and divergent nature of C4 evolution. Examining the evolutionary history of these cell-type-specific ACRs revealed a spectrum of conserved and novel ACRs, even among closely related species, indicating ongoing evolution of cis-regulation at these C4 loci. This study illuminates the dynamic and complex nature of CRE evolution in C4 photosynthesis, particularly highlighting the intricate cis-regulatory evolution of key loci. Our findings offer a valuable resource for future investigations, potentially aiding in the optimization of C3 crop performance under changing climatic conditions.

plant biology↗

bioRxiv2023

A barley MLA receptor is targeted by a non-ribosomal peptide effector of the necrotrophic spot blotch fungus for disease susceptibility

The evolutionary history of plant interactions with necrotrophic pathogens that feed on dying host cells and their virulence mechanisms remains fragmentary. We have isolated the barley gene Scs6, which is required for the necrotrophic fungus Bipolaris sorokiniana isolate ND90Pr to cause spot blotch disease. Scs6 is located at the disease resistance gene locus Mildew locus a (Mla) and encodes an intracellular nucleotide-binding leucine-rich repeat receptor (NLR). In transgenic barley, Scs6 is sufficient to confer susceptibility to ND90Pr in accessions naturally lacking the receptor, resulting in infection-associated host cell death. Expression of Scs6 in evolutionarily distant Nicotiana benthamiana reconstitutes a cell death response to an uncharacterized non-ribosomal peptide effector produced by ND90Pr-specific non-ribosomal peptide synthetases (NRPSs) encoded at the VHv1 virulence locus. Our data suggest that the heat-resistant effector directly activates the SCS6 receptor. Scs6 is an allelic variant of functionally diversified Mla resistance genes each conferring strain-specific immunity to barley powdery mildew isolates with a matching proteinaceous pathogen effector. Domain swaps between MLA and SCS6 NLRs and expression of the resulting hybrid proteins in N. benthamiana reveal that the SCS6 leucine-rich repeat domain is a specificity determinant for the NRPS-derived effector to activate the receptor. Scs6 evolved after the divergence of barley from wheat and is maintained in several wild barley populations with an incidence of 8%, suggesting a beneficial function for the host. Evolution of the bona fide immune receptor SCS6 targeted by the NRPS-derived effector was key for the emergence of strain-specific spot blotch disease in domesticated barley.

plant biology↗

bioRxiv2023

Three-dimensional dipole orientation mapping with high temporal-spatial resolution using polarization modulation

Fluorescence polarization microscopy is widely used in biology for molecular orientation properties. However, due to the limited temporal resolution of single-molecule orientation localization microscopy and the limited orientation dimension of polarization modulation techniques, achieving simultaneous high temporal-spatial resolution mapping of the three-dimensional (3D) orientation of fluorescent dipoles remains an outstanding problem. Here, we present a super-resolution 3D orientation mapping (3DOM) microscope that resolves 3D orientation by extracting phase information of the six polarization modulation components in reciprocal space. 3DOM achieves an azimuthal precision of 2{degrees} and a polar precision of 3{degrees} with spatial resolution of 128 nm in the experiments. We validate that 3DOM not only reveals the heterogeneity of the milk fat globule membrane, but also elucidates the 3D structure of biological filaments, including the 3D spatial conformation of {lambda}-DNA and the structural disorder of actin filaments. Furthermore, 3DOM images the dipole dynamics of microtubules labeled with green fluorescent protein in live U2OS cells, reporting dynamic 3D orientation variations. Given its easy integration into existing wide-field microscopes, we expect the 3DOM microscope to provide a multi-view versatile strategy for investigating molecular structure and dynamics in biological macromolecules across multiple spatial and temporal scales.

molecular biology↗

bioRxiv2023

Vagus nerve stimulation by focused ultrasound attenuates acute myocardial ischemia/reperfusion injury predominantly through cholinergic anti-inflammatory pathway

BackgroundThe invasive method using electrically stimulating vagus nerve has been demonstrated to inhibit the inflammatory response against acute myocardial ischemia/reperfusion(I/R) injury. This neuro-regulatory technique used is invasive implantation of electrical stimulators which have the risk of infection and other complications. A non-invasive method of vagus nerve stimulation applying on acute myocardial I/R injury is particularly important and desirable. ObjectivesThis study aimed to test the hypothesis that focused ultrasound stimulation(FUS) of vagus nerve attenuates acute myocardial I/R injury through cholinergic anti-inflammatory pathway. MethodsThis study was completed with two parts. In the first part, ischemia was induced by left anterior descending coronary artery (LAD) occlusion for 30 minutes (min), followed by 2 hours (h) of reperfusion, FUS lasted for 50 min after reperfusion for 10 min. Infammatory markers, arrhythmia score, histopathology, infammatory markers 7 nicotinic acetylcholine receptor (7nAchR) protein were determined. In the second part, ischemia was induced by LAD occlusion for 30 min, followed by 24h of reperfusion, FUS lasted for 50 min after reperfusion for 10 min. Myocardial fibrosis, infarct size, echocardiographic measurements, biomarkers of pro-oxidative stress, antioxidant and myocardial apoptosis were determined. ResultsFUS of vagus nerve significantly decreased the level of infammatory markers in I/R+FUS group compared with the I/R group, I/R+vagotomy group and I/R+vagotomy+FUS group. FUS decreased the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF), while also reduced arrhythmia score in I/R+FUS group compared with the I/R group. These improvements were associated with the inhibition of acute inflammatory reaction through cholinergic anti-inflammatory pathway. FUS limited myocardial fibrosis and infarct size, preserved left ventricular function. This cardioprotective effect was associated with alleviation of apoptosis and oxidative stress. ConclusionsThe noninvasive method of ultrasonic neuromodulation using FUS of vagus nerve exerted protective effects on acute myocardial I/R injury. Its potential mechanisms involved the suppression of acute inflammatory reaction through cholinergic anti-inflammatory pathway.

neuroscience↗

bioRxiv2023

High-speed Auto-Polarization Synchronization Modulation Three-dimensional Structured Illumination Microscopy

In recent years, notable progress has been achieved in both the hardware and algorithms of structured illumination microscopy (SIM). Nevertheless, the advancement of 3DSIM has been impeded by challenges arising from the speed and intricacy of polarization modulation. In this study, we introduce a high-speed modulation 3DSIM system, leveraging the polarization maintaining and modulation capabilities of a digital micro-mirror device (DMD) in conjunction with an electro-optic modulator. The DMD-3DSIM system yields a 2-fold enhancement in both lateral (133 nm) and axial (300 nm) resolution compared to wide-field imaging, and can acquire a data set comprising 29 sections of 1024x1024 pixels, with 15 ms exposure time and 6.75 s per volume. The versatility of the DMD-3DSIM approach was exemplified through the imaging of various specimens, including fluorescent beads, nuclear pores, microtubules, actin filaments, and mitochondria within cells, as well as plant and animal tissues. Notably, polarized 3DSIM elucidated the orientation of actin filaments. Furthermore, the implementation of diverse deconvolution algorithms further enhances three-dimensional resolution. The DMD-based 3DSIM system presents a rapid and reliable methodology for investigating biomedical phenomena, boasting capabilities encompassing 3D superresolution, fast temporal resolution, and polarization imaging.

cell biology↗

bioRxiv2023

Computational mechanism underlying switching of motor plans

Surviving in a constantly changing environment requires not only the ability to select actions, but also the flexibility to stop and switch actions when necessary. Extensive research has been devoted to understanding how the brain switches actions, yet the computations underlying switching and how it relates to selecting and stopping processes remain elusive. A central question is whether switching is an extension of the stopping process or involves different mechanisms. To address this question, we modeled action regulation tasks with a neurocomputational theory and evaluated its predictions on individuals performing reaches in a dynamic environment. Our findings suggest that, unlike stopping, switching does not necessitate a proactive pause mechanism to delay movement onset. However, switching engages a pause mechanism after movement onset, if the new target location is unknown prior to switch signal. These findings offer a new understanding of the action-switching computations, opening new avenues for future neurophysiological investigations.

neuroscience↗

bioRxiv2023

Targeting cancer with small molecule pan-KRAS degraders

Despite the high prevalence of cancers driven by KRAS mutations, to date only the G12C mutation has been clinically proven to be druggable via covalent targeting of the mutated cysteine amino acid residue (1). However, in many cancer indications other KRAS mutations, such as G12D and -V, are far more prevalent and small molecule concepts that can address a wider variety of oncogenic KRAS alleles are in high clinical demand (2). Here we show that a single small molecule can be used to simultaneously and potently degrade 13 out of 17 of the most prevalent oncogenic KRAS alleles, including those not yet tractable by inhibitors. Compared with inhibition, degradation of oncogenic KRAS results in more profound and sustained pathway modulation across a broad range of KRAS mutant cell lines. As a result, KRAS degraders inhibit growth of the majority of cancer cell lines driven by KRAS mutations while sparing models without genetic KRAS aberrations. Finally, we demonstrate that pharmacological degradation of oncogenic KRAS leads to tumour regression in vivo. Together, these findings unveil a new path towards addressing KRAS driven cancers with small molecule degraders. One-Sentence SummaryThe most prevalent KRAS variants which drive tumour growth in a major share of cancer patients can be targeted with a single small molecule degrader.

pharmacology and toxicology↗

bioRxiv2023

Comparison of image registration techniques in functional ultrasound imaging

Functional Ultrasound Imaging (fUSI) is an emerging hemodynamic-based functional neuroimaging technique that combines high spatiotemporal resolution and sensitivity, as well as extensive brain coverage, enabling a range of applications in both control and disease animal models. Based on power Doppler (pD) imaging, fUSI measures changes in cerebral blood volume (CBV) by detecting the back-scattered echoes from red blood cells moving within its field of view (FOV). However, the expansion of fUSI technology is partly limited by the challenge to co-register pD vascular maps acquired across different sessions or animals to one reference; an approach that could widen the scope of experimental paradigms and enable advanced data analysis tools. In this study, we seek to address this critical limitation. We evaluate six image registration techniques, predominantly used in other neuroimaging studies, using 2D sagittal whole-brain fUSI data from 82 anesthetized mice, and tested the quality of registration using multiple metrics. Our findings indicate a substantial enhancement in the alignment of fUSI images post registration. Among the tested techniques, the non-rigid registration algorithm Imregdeform yielded superior performance. We offer the first comparative study of image registration techniques for a 2D fUSI brain dataset, paving a way for improved utilization of fUSI in future pre-clinical research applications.

neuroscience↗

bioRxiv2023

Joint profiling of multiplex chromatin interactions, gene expression, and RNA-chromatin associations in single cells of the human brain

SUMMARY PARAGRAPHThe dynamically organized chromatin complexes often involve multiplex chromatin interactions and sometimes chromatin-associated RNA (caRNA) 1-3. Chromatin complex compositions change during cellular differentiation and aging, and are expected to be highly heterogeneous among terminally differentiated single cells 4-7. Here we introduce the Multi-Nucleic Acid Interaction Mapping in Single Cell (MUSIC) technique for concurrent profiling of multiplex chromatin interactions, gene expression, and RNA-chromatin associations within individual nuclei. Applied to 14 human frontal cortex samples from elderly donors, MUSIC delineates diverse cortical cell types and states. We observed the nuclei exhibiting fewer short-range chromatin interactions are correlated with an "older" transcriptomic signature and with Alzheimers pathology. Furthermore, the cell type exhibiting chromatin contacts between cis expression quantitative trait loci (cis eQTLs) and a promoter tends to be the cell type where these cis eQTLs specifically affect their target genes expression. Additionally, the female cortical cells exhibit highly heterogeneous interactions between the XIST non-coding RNA and Chromosome X, along with diverse spatial organizations of the X chromosomes. MUSIC presents a potent tool for exploring chromatin architecture and transcription at cellular resolution in complex tissues.

genomics↗