Biology subjects

Zhong, J.

Publications and source records attributed to Zhong, J..

143 records · Page 8Linked to original sources

bioRxiv2020

Integrated profiling of single cell epigenomic and transcriptomic landscape of Parkinson's disease mouse brain

Parkinsons disease (PD) is a neurodegenerative disease leading to the impairment of execution of movement. PD pathogenesis has been largely investigated, but either restricted in bulk level or at certain cell types, which failed to capture cellular heterogeneity and intrinsic interplays among distinct cell types. To overcome this, we applied single-nucleus RNA-seq and single cell ATAC-seq on cerebellum, midbrain and striatum of PD mouse and matched control. With 74,493 cells in total, we comprehensively depicted the dysfunctions under PD pathology covering proteostasis, neuroinflammation, calcium homeostasis and extracellular neurotransmitter homeostasis. Besides, by multi-omics approach, we identified putative biomarkers for early stage of PD, based on the relationships between transcriptomic and epigenetic profiles. We located certain cell types that primarily contribute to PD early pathology, narrowing the gap between genotypes and phenotypes. Taken together, our study provides a valuable resource to dissect the molecular mechanism of PD pathogenesis at single cell level, which could facilitate the development of novel methods regarding diagnosis, monitoring and practical therapies against PD at early stage.

cell biology↗

bioRxiv2020

Single cell atlas of trisomy 21 cerebral cortex

Down syndrome (DS) is one of the most common human birth defects caused by trisomy 21 (T21), leading to a variety of cognitive impairments. The cellular composition of human brain has been explored using single cell RNA sequencing in both physiological and pathological conditions. However, the cellular heterogeneity of human brain with chromosome aneuploidy is largely unknown. Here, we profiled the transcriptome of 36046 cells in cerebral cortex of T21 human fetus, covering frontal lobe, parietal lobe, occipital lobe and temporal lobe. Intriguingly, we detected several genes positively associated with neurons maturation was dysregulated in T21 frontal cortex (HIC2, POU2F2, ZGLP1 and FOXK1). To share, explore and utilized the data resources of T21 cerebral cortex, we developed a comprehensive platform named T21atlas, composing of two functional modules (T21cluster and T21talk). Overall, our study provides, as far as we know, the first single cell atlas for T21 cerebral cortex, which could promote our understanding of the molecular mechanism of DS at an unprecedented resolution and could potentially facilitate the development of novel clinical therapeutics against T21.

neuroscience↗

bioRxiv2019

Single cell atlas of domestic pig brain illuminates the conservation and divergence of cell types at spatial and species levels

Domestic pig (Sus scrofa domesticus) has drawn much attention from researchers worldwide due to its implications in evolutionary biology, regenerative medicine and agriculture. The brain atlas of Homo sapiens (primate), Mus musculus (rodent), Danio rerio (fish) and Drosophila melanogaster (insect) have been constructed at single cell resolution, however, the cellular compositions of pig brain remain largely unexplored. In this study, we investigated the single-cell transcriptomic profiles of five distinct regions of domestic pig brain, from which we identified 21 clusters corresponding to six major cell types, characterized by unique spectrum of gene expression. By spatial comparison, we identified cell types enriched or depleted in certain brain regions. Inter-species comparison revealed cell-type similarities and divergences in hypothalamus between mouse and pig, providing invaluable resources for the evolutionary exploration of brain functions at single cell level. Besides, our study revealed cell types and molecular pathways closely associated with several diseases (obesity, anorexia, bulimia, epilepsy, intellectual disability, and autism spectrum disorder), bridging the gap between gene mutations and pathological phenotypes, which might be of great use to the development precise therapies against neural system disorders. Taken together, we reported, so far as we know, the first single cell brain atlas of Sus scrofa domesticus, followed by comprehensive comparisons across brain region and species, which could throw light upon future evo-devo, regenerative medicine, and agricultural studies.

bioinformatics↗

bioRxiv2019

Diffusion Weighted Image Co-registration: Investigation of Best Practices

1.The registration or alignment of diffusion weighted images (DWI) with other imaging modalities is a critical step in neuroimaging analysis. Within-subject T1-DWI co-registration is particularly instrumental. DWI-derived scalar images are commonly used as intermediates for T1-DWI co-registration, and the resulting registration transforms are applied to all other scalar images for analysis. The ideal registration intermediate should register well to T1 and other multimodal images and be practically easy to obtain. It is however, currently unclear which DWI-derived scalar image serves as the best intermediate. We aim to determine the best, practical, intermediate for image co-registration. T1 and DWI images were acquired from 20 healthy subjects. DWIs were acquired with 60 directions. Six DWI-derived scalar images were compared including: 1) fractional anisotropy (FA); 2) generalized FA (GFA); 3) B0 images; 4) mean DWIs with the B0 image (MDWI); 5) anisotropic power (AP) images. AP showed the smallest variability in registration improvements across all the tested DWI derived scalar images, and show the highest average percent changes with CC registration cost function (CC=1.2%, MI=15%). In contrast, the FA and GFA transforms resulted in significantly poorer registration across DWI types. The AP image was the DWI-derived scalar image that provided the most consistent registration to all other images. Practically, it is generated easily and so could be implemented in basic and clinical research pipelines currently using other intermediates. Given these findings, it is recommended that AP images be used for T1-DWI co-registration, and that FA and GFA images in particular be avoided.

neuroscience↗

bioRxiv2019

Variations of gut microbiome profile under different storage conditions and preservation periods: A multi-dimensional evaluation

Gut dysbiosis contributes to the development of various human diseases. There are thousands of publications per year for investigating the role of gut microbiota in development of various diseases. However, emerging evidence has indicated data inconsistency between different studies frequently, but gained very little attention by scientists. There are many factors that can cause data variation and inconsistency during the process of microbiota study, in particular, sample storage conditions and subsequent sequencing process. Here, we systemically evaluated the impacts of six fecal sample storage conditions (including -80 {degrees}C, -80 {degrees}C with 70% ethanol (ET_-80 {degrees}C), 4{degrees}C with 70% ethanol (ET_4{degrees}C), and three commercial storage reagents including OMNIgene*GUT OMR-200 (GT), MGIEasy (MGIE), and Longsee (LS)), storage periods (1, 2 weeks or 6 months), and sequencing platform on gut microbiome profile using 16S rRNA gene sequencing. Our results suggested that -80{degrees}C is acceptable for fecal sample storage, and the addition of 70% ethanol offers some benefits. Meanwhile, we found that samples in ET_4 {degrees}Cand GT reagents are comparable, both introduced multi-dimensional variations. The use of MGIE resulted in the least alteration, while the greatest changes were observed in samples stored in LS reagents during the whole experiment. Finally, we also confirmed that variations caused by storage condition were larger than that of storage time and sequencing platform.\n\nIMPORTANCEIn the current study, we performed a multi-dimensional evaluation on the variations introduced by types of storage conditions, preservation period and sequencing platform on the basis of data acquired from 16S rRNA gene sequencing. The efficacy of preservation methods was comprehensively evaluated by DNA yield and quality, and {beta} diversity, relative abundance of the dominant bacteria and functional bacteria associated with SCFAs producing and BAs metabolism. Our results confirmed that variations introduced by storage condition were larger than that of storage periods and sequencing platform. Collectively, our study provided a comprehensive view to the impacts of storage conditions, storage times, and sequencing platform on gut microbial profile.

microbiology↗

bioRxiv2019

Inhibition of ADORA1 attenuates hepatic steatosis by gut microbiota-derived acetic acid from Astragalus polysaccharides

The authors have withdrawn this manuscript, because some data could not be replicated. During the process of subsequent revision of the manuscript, we separated the data into two parts. The majority data of the preprint draft, the anti-NAFLD effect of Astragalus polysaccharides (APS) in mice and the contribution of gut microbiota, were independently published in 2021 after substantial revision (doi: https://doi.org/10.1080/19490976.2021.1930874). However, the data on figure 6 (about ARs inhibitors DPCPX orally ameliorating NAFLD in mice, and Adora1 si-RNA data in vitro) could not be fully replicated in subsequent experiments. The most probable reason might be due to the batch differences of mice / cells, or other undetermined factors during experiment. Moreover, we have carried out in-depth studies on the exact role of hepatic A1R on NAFLD formation, which is opposite to our prior assumption. Therefore, we do not wish this work to be cited as reference for the project. We apologize for any inconvenience caused to our readers. Any questions can be addressed to first/corresponding author.

physiology↗

bioRxiv2019

Sing cell RNA-seq reveals cellular diversity and developmental characteristics of human infant retina

Retina, located in the innermost layer of the eye of human, holds the decisive role in visual perception. Dissecting the heterogeneity of retina is essential for understanding the mechanism of vision formation and even the development of central nervous system (CNS). Here, we performed single cell RNA-seq, analyzed 57,832 cells from human infant donors, resulting in 20 distinct clusters representing major cell types in retina: rod photoreceptors, cone photoreceptors, bipolar cells, horizontal cells, amacrine cells, Muller glia cells and microglia. We next constructed extensive networks of intercellular communication and identified ligand-receptor interactions playing crucial roles in regulating neural cell development and immune homeostasis in retina. Though re-clustering, we identified known subtypes in cone PRs and additional unreported subpopulations and corresponding markers in rod PRs as well as bipolar cells. Additionally, we linked inherited retinal disease to certain cell subtypes or subpopulations through enrichment analysis. Intriguingly, we found that status and functions of photoreceptors changed drastically between early and late retina. Overall, our study offers the first retinal cell atlas in human infants, dissecting the heterogeneity of retina and identifying the key molecules in the developmental process, which provides an important resource that will pave the way for retina development mechanism research and regenerative medicine concerning retinal biology.

cell biology↗

bioRxiv2019

Single cell RNA sequencing reveals cellular diversity of trisomy 21 retina

Retina is a crucial tissue for the capturing and processing of light stimulus. Characterization of the retina at single cell level is essential for the understanding of its biological functions. A variety of abnormalities in terms of morphology and function were reported in T21 retina. To evaluate the effects of chromosome aneuploidy on retina development, we characterized single cell transcriptional profiles of a T21 fetus and performed comprehensive bioinformatic analyses. Our data revealed the diversity and heterogeneity of cellular compositions in T21 retina. In total, we identified seven major cell types, and detected several subtypes within each cell type, followed by the detection of corresponding molecular markers including previously reported ones and a series of novel markers. Our analyses identified extensive communication networks between distinct cellular types, among which a few ligand-receptor interactions were associated with the development of retina and immunoregulatory interactions. Taken together, our data provided the first single cell transcriptome profile for human T21 retina which facilitates our understanding on the dosage effects of chromosome 21 on the development of retina.

cell biology↗

bioRxiv2019

Raven Calls Indicate Sender’s Neural State

Vocal communication accounts for dominantly percentage within animal species. The information of vocal samples contains not only the amplitude of objects, but also the emotional states behind it. However, to extract the emotion state behind the sound remains controversial. Here we introduce an artificial network method, the Back Propagation Neural Network, BPNN, to classify the emotional states behind the sound. The results disclosed the behaviour categories, including alarm, flight, begging and singing which has been successfully classified. This artificial intelligence classification may aid us to distinguish the ecological categories via animal vocal communication and to discover its significance of evolution and nature.

bioengineering↗

bioRxiv2019

FabriEVEs: A dedicated platform for endogenous viral elements in fishes, amphibians, birds, reptiles and invertebrates

Endogenous viral elements (EVEs) are heritable viral deriving elements present in the genomes of other species. As DNA fossils left by ancient viruses, EVEs were used to infer the characteristics of extinct viruses. EVEs in mammals have been well classified by several databases, however, EVEs in non-mammalian organisms are poorly documented. Here, we report FabriEVEs (http://tfbsbank.co.uk/FabriEVEs), the first dedicated and comprehensive online platform for the collection, classification and annotation of EVEs in fishes, amphibians, birds, reptiles and invertebrates. In total, nearly 1.5 million EVEs from 82 species deriving from class I (dsDNA), II (ssDNA), III (dsRNA), IV (positive ssRNA), V (negative ssRNA), VI (ssRNA-RT) and VII (dsDNA-RT) viruses were recorded in FabriEVEs, accompanying with comprehensive annotation including the species name, location, genomic features, virus family and associated literature. Flexible and powerful query options were provided to pinpoint desired EVEs. Furthermore, FabriEVEs provides free access to all EVEs data in case users need to download them for further analysis. Taken together, our database provided systematic classification and annotation of EVEs in non-mammal species, which paves the way for comparative analysis of EVEs and throws light upon the co-evolution of EVEs and their hosts.

evolutionary biology↗

bioRxiv2019

A molecular phylogeny of Schizothoracinae (Teleostei: Cypriniformes: Cyprinidae) based on 12 protein-coding mitochondrial genes and RAG1 gene analysis

The ever-increasing interest in the investigation of origin and speciation of schizothoracine fishes can be dated to 20th century. However, molecular phylogeny of Schizothoracinae and their phylogenetic relationships, as well as the divergence times still remain controversial. In this study, two DNA sets consisting of 12 protein-coding mitochondrial genes from 254 individuals and RAG1 gene from 106 individuals were used to reconstruct the phylogenetic relationships and calculate the divergence times among the subfamily schizothoracinae. Our results indicated that both of the data sets supported a non-monophyletic relationship due to involving of species of Barbinae. However, the phylogenetic relationships based on mtDNA genes were more reliable than that inferred from RAG1 gene. The highly specialized grade formed a monophyletic group, together with Ptychobarbus as a sister group of Diptychus and Gymnodiptychus, which was belonging to specialized grade, indicating that Ptychobarbus may be transition species to involve to highly specialized schizothoracianae. In addition, the primitive grade clustered with Percocypris pingi, a species of Barbinae. Based on mtDNA gene, the speciation time of Schizothoracinae was 66 Ma, and the divergence time of the primitive grade and Percocypris pingi was 64 Ma. The speciation times of the three grades Schizothoracinae were 57 Ma, 51 Ma and 43 Ma, respectively; and the divergence time of specialized and highly specialized grade was 46 Ma. The divergence times of three grades were not consistent with the three stages of uplift of Qinghai-Tibet Plateau, which is older than the times.

molecular biology↗

bioRxiv2018

Characterization of DNA hydroxymethylation in hypothalamus of elderly mice with postoperative cognitive dysfunction

Postoperative cognitive dysfunction (POCD) is a common syndrome with perioperative cerebral damage in elderly patients, displaying cognitive impairment and memory loss. Current studies revealed that anesthesia is one of the important causes for POCD occurrence. Recently, Ubiquitin-like with PHD and Ring Finger Domains 2 (Uhrf2) has been reported to play a crucial role in regulating DNA methylation and hydroxymethylation, which are closely connected with memory building and erasure. However, whether narcotic drugs can affect Uhrf2 to impact on DNA methylation and hydroxymethylation in POCD is poorly understood. In this study, we established the elderly POCD mouse model through sevoflurane treatment, and observed the compromised levels of global DNA hydroxymethylated cytosine (5hmC) and Uhrf2 in hippocampus and amygdaloid nucleus compared to non-POCD and control. Furthermore, 5hmC modification on the promoters of the genes associated with neural protection and development, such as GDNF, BDNF, GCR, ACSS2 were reduced in the hippocampus of POCD compared to non-POCD and control groups by MedIP qPCR. Taken together, our findings determined that the loss of 5hmC in hippocampus and amygdaloid nucleus modulated by Uhrf2 suppression might result in the learning and memory ability impairment in POCD.

neuroscience↗

bioRxiv2018

Deficient FGF signaling in the developing peripheral retina disrupts ciliary margin development and causes aniridia

The mammalian ciliary margin is a part of the developing peripheral neural retina that differentiates into the ciliary body and the iris. Canonical WNT signaling plays a critical role in the specification of the ciliary margin at the peripheral retina in the presence of strong FGF signaling in the central retina. The mechanism of how the boundary between the central retina and the ciliary margin is created has not been previously elucidated. Using genetic ablation and epistasis experiments, we show that loss of FGF signaling gradient in the peripheral retina causes expansion of WNT signaling towards the central retina thereby disrupting the neurogenic boundary and compartmentalization of the ciliary margin. Loss of WNT signaling displays a complimentary effect with expansion of FGF signaling into the ciliary marginal space. Using in vivo experiments, we elucidate the FGF signaling cascade involved in development of the ciliary margin. We also identify the surface ectoderm as the source of WNT ligands in eliciting WNT response at the ciliary margin. We show that an interaction between FGF and WNT signaling is required for generation of the ciliary marginal cells. Taken together, our results reveal that a gradient intersection of FGF and WNT signaling is required for specification of the ciliary margin.

developmental biology↗

bioRxiv2018

Strain maps characterize the symmetry of convergence and extension patterns during Zebrafish gastrulation

During gastrulation of the zebrafish embryo, the cap of blastoderm cells organizes into the axial body plan of the embryo with left-right symmetry and head-tail, dorsal-ventral polarities. Our labs have been interested in the mechanics of early development and have investigated whether these large-scale cells movements can be described as tissue-level mechanical strain by a tectonics-based approach. The first step is to image the positions of all nuclei from mid-epiboy to early segmentation by digital sheet light microscopy (DSLM), organize the surface of the embryo into multi-cell spherical domains, construct velocity fields from the movements of these domains and extract 3D strain rate maps. Tensile/expansive and compressive strains in the axial and equatorial directions are detected during gastrulation as anterior and posterior expansion along the anterior-posterior axis and medial-lateral compression across the dorsal-ventral axis corresponding to convergence and extension. In later stages in development are represented by localized medial expansion at the onset of segmentation and anterior expansion at the onset of neurulation. Symmetric patterns of rotation are first detected in the animal hemispheres at mid-epiboly and then the vegetal hemispheres by the end of gastrulation. By analysing the temporal sequence of large scale movements, deformations across the embryo can be attributed to a combination of epiboly and dorsal convergence-extension.\n\nSignificanceStrain is an emergent property of tissues that originates from the mechanical coupling of cell-cell and cell-substrate interactions, individual cell shape changes, and cell level forces. By imaging the positions of nuclei from mid-epiboly to early segmentation of the zebrafish embryo we are able to calculate three types of strain maps by a plate tectonics based method. The regions of expansive and compressive axial and equatorial strain correspond to areas undergoing convergence and extension, a major step in the formation of the embryonic body plan as well as the formation of somite and head structures. The most striking signatures of strain are: 1. the bilateral symmetry of linear strain across the anterior-posterior, dorsal-ventral axis during gastrulation, 2. the complementary counter-rotational strains or curl in the animal hemisphere at mid epiboly, and 3. a divergence or saddle point in the region of the dorsal organizer, head-trunk boundary. These strains represent a general method to describe large-scale tissue-level mechanics not only of embryonic development but also tissue homeostasis and disease.

biophysics↗

bioRxiv2018

Single-cell RNA-seq reveals dynamic transcriptome profiling in human early neural differentiation

BackgroundInvestigating cell fate decision and subpopulation specification in the context of the neural lineage is fundamental to understanding neurogenesis and neurodegenerative diseases. The differentiation process of neural-tube-like rosettes in vitro is representative of neural tube structures, which are composed of radially organized, columnar epithelial cells and give rise to functional neural cells. However, the underlying regulatory network of cell fate commitment during early neural differentiation remains elusive.\n\nResultsIn this study, we investigated the genome-wide transcriptome profile of single cells from six consecutive reprogramming and neural differentiation time points and identified cellular subpopulations present at each differentiation stage. Based on the inferred reconstructed trajectory and the characteristics of subpopulations contributing the most towards commitment to the central nervous system (CNS) lineage at each stage during differentiation, we identified putative novel transcription factors in regulating neural differentiation. In addition, we dissected the dynamics of chromatin accessibility at the neural differentiation stages and revealed active c/s-regulatory elements for transcription factors known to have a key role in neural differentiation as well as for those that we suggest are also involved. Further, communication network analysis demonstrated that cellular interactions most frequently occurred among embryoid body (EB) stage and each cell subpopulation possessed a distinctive spectrum of ligands and receptors associated with neural differentiation which could reflect the identity of each subpopulation.\n\nConclusionsOur study provides a comprehensive and integrative study of the transcriptomics and epigenetics of human early neural differentiation, which paves the way for a deeper understanding of the regulatory mechanisms driving the differentiation of the neural lineage.

developmental biology↗

bioRxiv2018

Ancestry of the two subgenomes of maize

Maize (Zea mays ssp. mays) is not only one of the worlds most important crops, but it also is a powerful tool for studies of genetics, genomics, and cytology. The genome of maize shows the unmistakable signature of an ancient hybridization event followed by whole genome duplication (allopolyploidy), but the parents of this event have been a mystery for over a century, since studies of maize cytogenetics began. Here we show that the whole genome duplication event preceded the divergence of the entire genus Zea and its sister genus Tripsacum. One genome was donated, in whole or in part, by a plant related to the modern African genera Urelytrum and Vossia, although genomic rearrangement has been extensive. The other genome donor is less well-supported, but may have been related to the modern Rottboellia-Hemarthria clade, which is also African. Thus Zea and Tripsacum together represent a New World radiation derived from African ancestors.

plant biology↗

bioRxiv2016

Tractography-based connectomes are dominated by false-positive connections

Fiber tractography based on non-invasive diffusion imaging is at the heart of connectivity studies of the human brain. To date, the approach has not been systematically validated in ground truth studies. Based on a simulated human brain dataset with ground truth white matter tracts, we organized an open international tractography challenge, which resulted in 96 distinct submissions from 20 research groups. While most state-of-the-art algorithms reconstructed 90% of ground truth bundles to at least some extent, on average they produced four times more invalid than valid bundles. About half of the invalid bundles occurred systematically in the majority of submissions. Our results demonstrate fundamental ambiguities inherent to tract reconstruction methods based on diffusion orientation information, with critical consequences for the approach of diffusion tractography in particular and human connectivity studies in general.

neuroscience↗