Biology subjects

Zhu, T.

Publications and source records attributed to Zhu, T..

At least 91 records · Page 5Linked to original sources

bioRxiv2023

DPHL v2: An updated and comprehensive DIA pan-human assay library for quantifying more than 14,000 proteins.

A comprehensive pan-human spectral library is critical for biomarker discovery using mass spectrometry (MS)-based proteomics. DPHL v1, a previous pan-human library built from 1096 data-dependent acquisition (DDA) MS data of 16 human tissue types, allows quantifying 10,943 proteins. However, a major limitation of DPHL v1 is the lack of semi-tryptic peptides and protein isoforms, which are abundant in clinical specimens. Here, we generated DPHL v2 from 1608 DDA-MS data acquired using Orbitrap mass spectrometers. The data included 586 DDA-MS newly acquired from 17 tissue types, while 1022 files were derived from DPHL v1. DPHL v2 thus comprises data from 24 sample types, including several cancer types (lung, breast, kidney, and prostate cancer, among others). We generated four variants of DPHL v2 to include semi-tryptic peptides and protein isoforms. DPHL v2 was then applied to a publicly available colorectal cancer dataset with 286 DIA-MS files. The numbers of identified and significantly dysregulated proteins increased by at least 21.7% and 14.2%, respectively, compared with DPHL v1. Our findings show that the increased human proteome coverage of DPHL v2 provides larger pools of potential protein biomarkers.

bioinformatics↗

bioRxiv2023

The mechanosensitive ion channel Piezo1 contributes to ultrasound neuromodulation

Transcranial low-intensity ultrasound is a promising neuromodulation modality, with the advantages of non-invasiveness, deep penetration, and high spatiotemporal accuracy. However, the underlying biological mechanism of ultrasonic neuromodulation remains unclear, hindering the development of efficacious treatments. Here, the well-known Piezo1, was studied through a conditional knockout mouse model as a major molecule for ultrasound neuromodulation ex vivo and in vivo. We showed that Piezo1 knockout in the right motor cortex of mice significantly reduced ultrasound-induced neuronal calcium responses, limb movement and muscle EMG responses. We also detected higher Piezo1 in the central amygdala (CEA) which were found more sensitive to ultrasound stimulation than that of cortex. Knocking out the Piezo1 in CEA neurons showed a significant reduction of response under ultrasound stimulation while knocking out astrocytic Piezo1 showed no obvious changes in neuronal responses. Additionally, we excluded an auditory confound by monitoring auditory cortical activation and using smooth waveform ultrasound with randomized parameters to stimulate P1KO ipsilateral and contralateral regions of the same brain and recording evoked movement in the corresponding limb. Thus, we demonstrate that Piezo1 is functionally expressed in different brain regions, and that it is an important mediator of ultrasound neuromodulation in the brain, laying the ground for further mechanistic studies of ultrasound.

neuroscience↗

bioRxiv2022

Different low-complexity regions of SFPQ play distinct roles in the formation of biomolecular condensates

Demixing of proteins and nucleic acids into condensed liquid phases is rapidly emerging as a ubiquitous mechanism governing the organisation of molecules within the cell. Long disordered low complexity regions (LCRs) are a common feature of proteins that form biomolecular condensates. RNA-binding proteins with prion-like composition have been highlighted as drivers of liquid demixing to form condensates such as nucleoli, paraspeckles and stress granules. Splicing factor proline- and glutamine-rich (SFPQ) is an RNA- and DNA-binding protein essential for DNA repair and paraspeckle formation. Here, we show that the shorter C-terminal LCR of SFPQ is the main region responsible for the condensation of SFPQ in vitro and in the cell. In contrast, we find that, unexpectedly, the longer N-terminal prion-like LCR of SFPQ attenuates condensation, suggesting a more regulatory role in preventing aberrant condensate formation in the cell. Our data add nuance to the emerging understanding of biomolecular condensate formation, by providing the first example of a common multifunctional nucleic acid-binding protein with an extensive prion-like region that serves to regulate rather than drive condensate formation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/518278v2_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@ed464dorg.highwire.dtl.DTLVardef@1a26fdcorg.highwire.dtl.DTLVardef@15debecorg.highwire.dtl.DTLVardef@12bd4ae_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2022

Organization, genomic targeting and assembly of three distinct SWI/SNF chromatin remodeling complexes in Arabidopsis

Switch defective/sucrose non-fermentable (SWI/SNF) complexes are evolutionarily conserved multi-subunit machines that play vital roles in chromatin architecture regulation for modulating gene expression via sliding or ejection of nucleosomes in eukaryotes. In plants, perturbations of SWI/SNF subunits often result in severe developmental disorders. However, the subunit composition, pathways of assembly, and genomic targeting of the plant SWI/SNF complexes remain undefined. Here, we reveal the organization, genomic targeting and assembly of three distinct Arabidopsis SWI/SNF complexes: BRAHMA-Associated SWI/SNF complexes (BAS), SPLAYED-Associated SWI/SNF complexes (SAS) and MINUSCULE-Associated SWI/SNF complexes (MAS). We show that BAS complexes are equivalent to human ncBAF, whereas SAS and MAS complexes evolve in multiple subunits unique to plants, suggesting a plant-specific functional evolution of SWI/SNF complexes. We further demonstrate overlapping and specific genomic targeting of the three plant SWI/SNF complexes on chromatin and reveal that SAS complexes are necessary for the correct genomic localization of the BAS complexes. Finally, we define the role of core module subunit in the assembly of the plant SWI/SNF complexes and highlight that ATPase module subunit is required for global complex stability and the interaction of core module subunits in SAS and BAS complexes in Arabidopsis. Together, our work highlights the divergence of SWI/SNF chromatin remodelers during the eukaryote evolution and provides a comprehensive landscape for understanding the plant SWI/SNF complexes organization, assembly, genomic targeting, and function. One-sentence summaryComprehensively define the organization, genomic targeting and assembly of three distinct SWI/SNF chromatin remodeling complexes in Arabidopsis

plant biology↗

bioRxiv2022

Calcitic prisms of the giant seashell Pinna nobilis form light guide arrays

The shells of the Pinnidae family are based on a double layer of single-crystal-like calcitic prisms and inner aragonitic nacre, a structure known for its outstanding mechanical performance. However, on the posterior side, shells are missing the nacreous layer, which raises the question of whether there could be any functional role in giving up this mechanical performance. Here, we demonstrate that the prismatic part of the Pinna nobilis shell exhibits unusual optical properties, whereby each prism acts as an individual optical fiber guiding the ambient light to the inner shell cavity by total internal reflection. This pixelated light channeling enhances both spatial resolution and contrast while reducing angular blurring, an apt combination for acute tracking of a moving object. Our findings may offer insights into the evolutionary aspects of light-sensing and imaging by biological materials and introduce a conceptual framework for the development of bio-inspired multifunctional ceramics and architectured light-tracking materials.

biophysics↗

bioRxiv2022

Real-Time Spatial Registration for 3D Human Atlas

AO_SCPLOWBSTRACTC_SCPLOWThe human body is made up of about 37 trillion cells (adults). Each cell has its own unique role and is affected by its neighboring cells and environment. The NIH Human BioMolecular Atlas Program (HuBMAP) aims at developing a 3D atlas of human body consisting of organs, vessels, tissues to singe cells with all 3D spatially registered in a single 3D human atlas using tissues obtained from normal individuals across a wide range of ages. A critical step of building the atlas is to register 3D tissue blocks in real-time to the right location of a human organ, which itself consists of complex 3D substructures. The complexity of the 3D organ model, e.g., 35 meshes for a typical kidney, poses a significant computational challenge for the registration. In this paper, we propose a comprehensive framework TICKET (TIssue bloCK rEgisTration) for tissue block registration for 3D human atlas, including (1) 3D mesh pre-processing, (2) spatial queries on intersection relationship and (3) intersection volume computation between organs and tissue blocks. To minimize search space and computation cost, we develop multi-level indexing on both the anatomical structure level and mesh level, and utilize OpenMP for parallel computing. Considering cuboid based shape of the tissue block, we propose an efficient voxelization-based method to estimate the intersection volume. Our experiments demonstrate that the proposed framework is practical and efficient. TICKET is now integrated into the HuBMAP CCF registration portal [1].

bioinformatics↗

bioRxiv2022

The effector recognition by synthetic sensor NLR receptors requires the concerted action of multiple interfaces within and outside the integrated domain

Plant sensor nucleotide-binding leucine-rich repeat (NLR) receptors detect pathogen effectors through their integrated domains (IDs). The RGA5 sensor NLR recognizes its corresponding effectors AVR-Pia and AVR1-CO39 from the blast fungus Magnaporthe oryzae through direct binding to its heavy metal-associated (HMA) ID to trigger the RGA4 helper NLR-dependent resistance in rice. Here we report a mutant of RGA5 named RGA5HMA5 that confers complete resistance in transgenic rice plants to the M. oryzae strains expressing the noncorresponding effector AVR-PikD. RGA5HMA5 carries three engineered interfaces, two of which lie in the HMA ID and the other in the C-terminal Lys-rich stretch tailing the ID. However, the RGA5 variants having one or two of the three interfaces, including replacing all the Lys residues with Glu residues in the Lys-rich stretch, failed to activate RGA4-dependent cell death of rice protoplasts. Altogether, this work demonstrates that sensor NLRs require a concerted action of multiple surfaces within and outside the IDs to both recognize noncorresponding effectors and activate helper NLR-mediated resistance, and has implications in structure-guided designing of sensor NLRs.

plant biology↗

bioRxiv2022

Potent Bacterial Vaccines Require FcγRIIB-mediated Pathogen Capture by Liver Sinusoidal Endothelium

Certain vaccines are more effective than others against microbial infections, but the molecular mechanisms separating the two types of vaccines are largely undefined. Here, by comparing two vaccines of Streptococcus pneumoniae with identical antigens but different efficacies (pneumococcal conjugate vaccine - PCV13 and pneumococcal polysaccharide vaccine - PPV23), we reveal that superior vaccine protection against blood-borne bacteria is primarily achieved by activating pathogen capture of the sinusoidal endothelial cells (ECs) in the liver. Consistent with its superior protection in humans, PCV13 confers a more potent protection than PPV23 against pneumococcal infection in mice. In vivo real-time imaging and genetic mutagenesis revealed that PCV13 activates both liver ECs and resident macrophages Kupffer cells (KCs) to capture IgG-coated bacteria via IgG Fc gamma receptor (Fc{gamma}R). In particular, the Fc{gamma}RIIB-mediated capture by ECs is responsible for PCV13-induced superior protection. In contrast, PPV23 only activates KCs (but not ECs) to achieve a less effective pathogen capture and protection through complement receptor-mediated recognition of IgM- and C3-coated bacteria. These liver-based vaccine protection mechanisms are also found with the vaccines of Neisseria meningitidis and Klebsiella pneumoniae, another two important invasive human pathogens. Our findings have uncovered a novel EC- and Fc{gamma}RIIB-mediated mechanism in the liver for more efficacious vaccine protection. These findings can serve as in vivo functional readouts to evaluate vaccine efficacy and guide the future vaccine development. One Sentence SummaryVaccine efficacy is defined by Fc{gamma}RIIB-mediated capture of antibody-coated bacteria via liver sinusoidal endothelial cells.

immunology↗

bioRxiv2022

Life cycle exposure to cyhalofop-butyl induced reproductive toxicity toward zebrafish

Cyhalofop-butyl (CyB) is an herbicide widely used in paddy fields, which may transfer to aquatic ecosystems and cause harm to aquatic organisms. In this study, zebrafish (Danio rerio) were exposed to CyB (0.1, 1 and 10 ug/L) related to the environment throughout its adult life cycle from embryo to sexual maturity. The effects of CyB on zebrafish growth, reproduction and offspring development were studied. It was found that female spawning was inhibited and adult male fertility decreased. In addition, we detected the expression of sex steroid hormones and genes related to hypothalamus-pituitary-gonad-liver (HPGL) axis. After 150days of exposure, the hormone balance of parent zebrafish (F0) was disturbed and the concentrations of 17{beta}-estradiol (E2) and vitellogenin (VTG) in zebrafish were decreased. F1 embryos showed abnormal developmental results, including decreased heart rate, decreased body length, spontaneous motor inhibition, while the developmental abnormalities of F1 embryos were relieved when exposed to CyB-free clear water. The change of sex hormone is regulated by gene expression related to HPGL axis. These results confirmed that long-term exposure to CyB in the environmental concentrations can damage the reproductive capacity of F0 generation zebrafish by disrupting the transcription of genes related to HPGL axis, which may lead to abnormal development of F1. Overall, these data may provide a new understanding of the reproductive toxicity of zebrafish parents and offspring after long-term exposure to CyB. HighlightsO_LIEnvironmental level of CyB exposure caused gonadal impairment. C_LIO_LICyB exposure suppressed spawning ability of zebrafish. C_LIO_LICyB exposure changed the plasma hormone level of zebrafish and altered HPGL axis in both genders. C_LIO_LIParental CyB exposure led to abnormal development of F1. C_LI

pharmacology and toxicology↗

bioRxiv2022

Mammary Tissue-Derived Extracellular Matrix Hydrogels Reveal the Role of the Irradiated Microenvironment in Breast Cancer Recurrence

Radiation therapy (RT) is essential for triple negative breast cancer (TNBC) treatment. However, patients with TNBC continue to experience recurrence after RT. The role of the extracellular matrix (ECM) of irradiated breast tissue in tumor recurrence is still unknown. In this study, we evaluated the structure, molecular composition, and mechanical properties of irradiated murine mammary fat pads (MFPs) and developed ECM hydrogels from decellularized tissues (dECM) to assess the effects of RT-induced ECM changes on breast cancer cell behavior. Irradiated MFPs were characterized by increased ECM deposition and fiber density compared to unirradiated controls, which may provide a platform for cell invasion and proliferation. ECM component changes in collagens I, IV, and VI, and fibronectin were observed following irradiation in both MFPs and dECM hydrogels. Encapsulated TNBC cell proliferation and invasive capacity was enhanced in irradiated dECM hydrogels. In addition, TNBC cells co-cultured with macrophages in irradiated dECM hydrogels induced M2 macrophage polarization and exhibited further increases in proliferation. Our study establishes that the ECM in radiation-damaged sites promotes TNBC invasion and proliferation as well as an immunosuppressive microenvironment. This work represents an important step toward elucidating how changes in the ECM after RT contribute to breast cancer recurrence.

cancer biology↗

bioRxiv2022

CvkR, a novel MerR-type transcriptional regulator, is a repressor of class 2 type V-K CRISPR-associated transposase systems

CRISPR-associated transposons (CASTs) exist in different groups of bacteria, including certain cyanobacteria, which contain type V-K CAST systems. These systems contain genes encoding Tn7-like transposase subunits and a divergent number of cargo genes. How the activity of these systems is controlled in situ has remained largely unknown but possibly regulatory genes within these elements are prime candidates. Deletion of the respective regulator gene alr3614 in the cyanobacterium Anabaena (Nostoc) sp. PCC 7120 led to the overexpression of CRISPR tracrRNA, precursor crRNAs and mRNAs encoding the Cas12k effector protein (all3613) and Tn7-like transposase subunits. Upon complementation, these same genes were repressed again. DNase I footprinting and electrophoretic mobility shift assays verified the direct interaction between Alr3614 and the promoter of cas12k and identified a widely conserved binding motif. Structural analysis of Alr3614 at 1.5 [A] resolution revealed that it belongs to the MerR-type transcription factor family but with distinct dimerization and effector-binding domains. This protein assembles into a homodimer interacting with DNA through its N-terminal winged helix-turn-helix (wHTH) domain and binds an effector molecule through a C-terminal -helical domain lacking a conserved cysteine. These results identify Alr3614 as a transcriptional repressor of the CAST system in Anabaena sp. PCC 7120. We suggest naming this family of repressors CvkR for Cas V-K repressors, which are at the core of a widely conserved regulatory mechanism that controls type V-K CAST systems.

microbiology↗

bioRxiv2022

MorphoGNN: Morphological Embedding for Single Neuron with Graph Neural Networks

With the development of optical imaging systems, neuroscientists can now obtain large datasets of morphological structure at a single neuron scale positioned across the whole mouse brain. However, the enormous amount of morphological data challenges the classic approach of neuron classification, indexing and other analysis tasks. In this paper, we propose MorphoGNN, a single neuron morphological embedding based on the graph neural networks (GNN). This method learns the spatial structure information between the nodes of reconstructed neuron fibers by its nearest neighbors on each layer and captures the lower-dimensional representation of a single neuron through an end-to-end model. This model is composed of densely connected edge convolution (EdgeConv) layers and a double pooling operator, regularized with joint cross-entropy loss and triplet loss. An increasing population of the neighbor nodes meets the need of learning more information with features expanding at the deep layer. We tested the proposed embeddings on the neuron classification and retrieval tasks. Our method achieves competitive performance both on the general point cloud dataset and the neuron morphology dataset.

neuroscience↗

bioRxiv2022

Tbx2 is essential for cochlear inner hair cell development and regeneration

Atoh1 is essential for the development of outer hair cells (OHCs) and inner hair cells (IHCs) in the mammalian cochlea. Whereas Ikzf2 is necessary for OHC development, the key gene for IHC development remains unknown. We found that deleting Tbx2 in neonatal IHCs led to their trans-differentiation into OHCs, by repressing 26.7% of IHC and inducing 56.3% of OHC genes, including Ikzf2. More importantly, persistent expression of Tbx2 together with transient Atoh1 effectively reprogramed non-sensory supporting cells into new IHCs expressing functional IHC marker vGlut3. The differentiation status of these new IHCs is much more advanced than those previously reported. Thus, Tbx2 is essential for IHC development, and its co-upregulation with Atoh1 in supporting cells represents a new approach for treating IHC degeneration-related deafness.

developmental biology↗

bioRxiv2022

Effects of Full-cycle Exposure to Difenoconazole in Parental Zebrafish on the Liver-gut Axis of F0 and F1 Generations

To explore the effects of long-term exposure to low-dose difenoconazole (DCZ) on lipid metabolism in the liver-gut axis, we exposed zebrafish embryos to ambient concentrations of DCZ for 120 days and comprehensively analyzed the metabolic and microbial networks of the F0 and F1 generations using biochemical, metabolomic and metagenomics approaches. The changes of biochemical indexes indicated that DCZ exposure inhibited lipid synthesis, lipolysis and lipid transport of F0 males and females. In addition, the composition of gut microbes in males and females was significantly changed, which corresponds to changes in biochemical parameters in liver, intestine and serum. Metabolome analysis showed that pathways related to amino acid metabolism, ATP-binding cassette transporters, carbohydrate metabolism, and energy metabolism were downregulated in the gut of males and females. At 120 days post-fertilization, lipid synthesis, lipolysis and lipid transport of F1 males was upregulated; the composition of microbiota and metabolome of the F1males gut was significantly altered. Overall, we found that long-term exposure to low doses of DCZ inhibited the liver-gut axis in males and females, and the liver-gut axis in F1 males were disturbed even in F1 generation without DCZ exposure.

bioinformatics↗

bioRxiv2022

Actin turnover protects the cytokinetic contractile ring from structural instability

In common with other actomyosin contractile cellular machineries, actin turnover is required for normal function of the cytokinetic contractile ring. Cofilin is an actin-binding protein contributing to turnover by severing actin filaments, required for cytokinesis by many organisms. In fission yeast cofilin mutants, contractile rings suffer bridging instabilities in which actin bundles peel away from the plasma membrane into straight bridges. The origin of this behaviour is unclear. Here we used molecularly explicit simulations of the fission yeast contractile ring to examine the role of cofilin. Simulations reproduced the experimentally observed cycles of bridging and reassembly during constriction, each lasting [~] 6 min, and the tendency for bridging to occur in ring segments with low myosin II Myo2 density. The lack of cofilin severing produced [~] 2-fold longer filaments and, consequently, [~] 2-fold higher ring tensions. Simulations identified bridging as originating in the boosted ring tension, which increased centripetal forces that detached actin from Myo2 that anchored actin to the membrane. Thus, cofilin serves a critical role in cytokinesis by protecting the contractile ring from bridging, the principal structural threat. Summary statementMolecularly explicit simulations showed that cofilin-mediated actin severing protects the fission yeast cytokinetic contractile ring from instabilities in which actin peels away into straight bridges.

cell biology↗

bioRxiv2022

Single-nucleus transcriptomic analysis reveals divergence of glial cells in peripheral somatosensory system between human and mouse

Glial cells play a crucial role in regulating physiological and pathological functions, such as sensation, infections, acute injuries, and chronic neurodegenerative disorders. Glial cells include astrocytes, microglia, and oligodendrocytes in the central nervous system (CNS) and satellite glial cells (SGCs) in the peripheral nervous system (PNS). Despite the understanding of glial subtypes and functional heterogeneity in animal models achieved by single-cell or single-nucleus RNA sequencing, no research has investigated the transcriptomic profiles of glial cells in the human PNS and spinal cord. Here, we used high-throughput single-nucleus RNA sequencing to map the cellular and molecular heterogeneity of SGCs in the human dorsal root ganglion (DRG) and astrocytes, microglia, and oligodendrocytes in the human spinal cord. To explore the conservation and divergence across species, we compared these human findings with those from mice. Additionally, the expression profiles of risk genes of common DRG and spinal cord diseases in glial cells were compared between humans and mice. As a result, little SGCs heterogeneity was found in both human and mouse DRG. In the human spinal cord, astrocytes, microglia, and oligodendrocytes were respectively divided into six distinct transcriptomic subclusters. In the mouse spinal cord, astrocytes, microglia, and oligodendrocytes were divided into six, five, and six distinct transcriptomic subclusters, respectively. The comparative results revealed substantial heterogeneity in all glial cells between humans and mice. Notably, we also identified transcriptomic heterogeneity in several classical genes and risk genes for neurological disorders across humans and mice. Together, the present data comprehensively profiled glial cell heterogeneity and provides a powerful resource for investigating the cellular basis of glial-related physiological and pathological conditions in peripheral somatosensory system.

neuroscience↗

bioRxiv2022

Study on gene knockout mice and human mutant individual reveals absence of CEP78 causes photoreceptor and sperm flagella impairments

BackgroundCone-rod dystrophy (CRD) is a genetically inherited retinal disease characterized by photoreceptor degeneration. In some rare cases, CRD and hearing loss can be associated with male fertility, while the underlying mechanism is not well known. MethodsUsing CRISPR/Cas9 system, we generated Cep78-/- mice. And electroretinogram (ERG), immunofluorescence staining and transmission electron microscopy (TEM) were used to analyze visual function and photoreceptor ciliary structure changes in Cep78-/- mouse. HE/PAS staining, scanning-electron microscopy (SEM) were conducted to Cep78-/- mice and human CRD patient with CEP78 protein loss to illustrate male infertility and multiple morphological abnormalities of the sperm flagella (MMAF) caused by CEP78 deficiency. TEM and immunofluorescence staining were performed to characterize morphological and molecular changes of sperm flagella microtubule arrangement, centriole development and spermatid head shaping in Cep78-/- mice. Mass-spectrometry analyses were conducted to identify protein abnormalities after Cep78 deletion and Cep78 interacting proteins in spermiogenesis. Co-immunoprecipitation was used to show the Cep78-Ift20-Ttc21a trimer. The role of Cep78-Ift20-Ttc21a trimer in cilliogenesis and centriole elongation was assessed by cilia induction assay. ResultsCep78 knockout mice exhibited impaired function and morphology of photoreceptors, typified by reduced electroretinogram amplitudes, disrupted translocation of cone arrestin, attenuated and disorganized photoreceptor outer segments (OS) disks and widen OS bases, as well as interrupted cilia elongations and structures. Cep78 deletion also caused male infertility and MMAF, with disordered "9 + 2" structure and triplet microtubules in sperm flagella. CEP78 forms a trimer with intraflagellar transport (IFT) proteins IFT20 and TTC21A essential for sperm flagella formation, is essential for their interaction and stability, and recruits IFT20 to centrosome. Insufficiency of any component in the trimer causes centriole elongation and cilia shortening. Additionally, absence of CEP78 protein in human leaded to similar phenotypes in vision and MMAF as Cep78-/- mice. ConclusionsWe found CEP78 as the causative gene of CRD with MMAF in human and mouse. Cep78 forms a trimer with Ift20 and Ttc21a, and regulate the interaction, stability and localization of the trimer proteins, which regulate cilliogenesis, centriole length, and sperm flagella formation. FundingThis work was supported by the National Key R&D Program (2021YFC2700200 to X.G); National Natural Science Foundation of China (82020108006, 81730025 to C.Z, 81971439, 81771641 to X.G, 82070974 to X.C, 82060183 to X.S); Shanghai Outstanding Academic Leaders (2017BR013 to C.Z); and Six Talent Peaks Project in Jiangsu Province (YY-019 to X.G). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

developmental biology↗

bioRxiv2022

A reference single-cell regulomic and transcriptomic map of cynomolgus monkeys

Non-human primates (NHP) are attractive laboratory animal models that accurately reflect both developmental and pathological features of humans. Here we present a compendium of cell types from the cynomolgus monkey Macaca fascicularis (denoted as Monkey Atlas) using both single-cell chromatin accessibility (scATAC-seq) and RNA sequencing (scRNA-seq) data at the organism-wide level. The integrated cell map enables in-depth dissection and comparison of molecular dynamics, cell-type composition and cellular heterogeneity across multiple tissues and organs. Using single-cell transcriptomic data, we inferred pseudotime cell trajectories and cell-cell communications to uncover key molecular signatures underlying their cellular processes. Furthermore, we identified various cell-specific cis-regulatory elements and constructed organ-specific gene regulatory networks at the single-cell level. Finally, we performed a comparative analysis of single-cell landscapes among mouse, cynomolgus monkey and human, and we showed that cynomolgus monkey has significantly higher degree of cell-type similarity to human than mouse. Taken together, our study provides a valuable resource for NHP cell biology.

bioinformatics↗