Biology subjects

Kong, S.

Publications and source records attributed to Kong, S..

46 records · Page 3Linked to original sources

bioRxiv2021

Comprehensive evaluation of ACE2 expression in female ovary by single-cell RNA-seq analysis

Pneumonia induced by severe acute respiratory coronavirus 2 (SARS-CoV-2) via ACE2 receptor may affect many organ systems like lung, heart and kidney. An autopsy report revealed positive SARS-Cov-2 detection results in ovary, however, the developmental-stage-specific and cell-type-specific risk in fetal primordial germ cells (PGCs) and adult women ovary remained unclear. In this study, we used single-cell RNA-sequencing (scRNA-seq) datasets spanning several developmental stages of ovary including PGCs and cumulus-oocyte complex (COC) to investigate the potential risk of SARS-CoV-2 infection. We found that PGCs and COC exhibited high ACE2 expression. More importantly, the ratio of ACE2-positive cells was sharply up-regulated in primary stage and ACE2 was expressed in all oocytes and cumulus cells in preovulatory stage, suggesting the possible risk of SARS-CoV-2 infection in follicular development. CatB/L, not TMPRSS2, was identified to prime for SARS-CoV-2 entry in follicle. Our findings provided insights into the potential risk of SARS-CoV-2 infection during folliculogenesis in adulthood and the possible risk in fetal PGCs.

developmental biology↗

bioRxiv2021

A sexual dimorphic role of the miR-465 cluster in placental development

A sexually dimorphic role of miRNAs in placental development has never been reported. Here, we show that ablation of the miR-465 cluster caused selective degeneration of female conceptuses as early as embryonic day (E)8.5, leading to a male-biased sex ratio (60% males) among miR-465 KO mice. Given that the miR-465 cluster miRNAs were predominantly expressed in the extraembryonic tissue and ablation of these miRNAs led to dysregulation of numerous critical placental genes, our data strongly suggest the miR-465 cluster is required for full developmental potential of the female, but not the male, extraembryonic tissue/placenta.

developmental biology↗

bioRxiv2020

Comparative Performance of Popular Methods for Hybrid Detection using Genomic Data

AO_SCPLOWBSTRACTC_SCPLOWInterspecific hybridization is an important evolutionary phenomenon that generates genetic variability in a population and fosters species diversity in nature. The availability of large genome scale datasets has revolutionized hybridization studies to shift from the examination of the presence or absence of hybrids in nature to the investigation of the genomic constitution of hybrids and their genome-specific evolutionary dynamics. Although a handful of methods have been proposed in an attempt to identify hybrids, accurate detection of hybridization from genomic data remains a challenging task. The available methods can be classified broadly as site pattern frequency based and population genetic clustering approaches, though the performance of the two classes of methods under different hybridization scenarios has not been extensively examined. Here, we use simulated data to comparatively evaluate the performance of four tools that are commonly used to infer hybridization events: the site pattern frequency based methods HyDe and the D-statistic (i.e., the ABBA-BABA test), and the population clustering approaches structure and ADMIXTURE. We consider single hybridization scenarios that vary in the time of hybridization and the amount of incomplete lineage sorting (ILS) for different proportions of parental contributions ({gamma}); introgressive hybridization; multiple hybridization scenarios; and a mixture of ancestral and recent hybridization scenarios. We focus on the statistical power to detect hybridization, the false discovery rate (FDR) for the D-statistic and HyDe, and the accuracy of the estimates of{gamma} as measured by the mean squared error for HyDe, structure, and ADMIXTURE. Both HyDe and the D-statistic demonstrate a high level of detection power in all scenarios except those with high ILS, although the D-statistic often has an unacceptably high FDR. The estimates of{gamma} in HyDe are impressively robust and accurate whereas structure and ADMIXTURE sometimes fail to identify hybrids, particularly when the proportional parental contributions are asymmetric (i.e., when{gamma} is close to 0). Moreover, the posterior distribution estimated using structure exhibits multimodality in many scenarios, making interpretation difficult. Our results provide guidance in selecting appropriate methods for identifying hybrid populations from genomic data.

bioinformatics↗

bioRxiv2020

Epigenetic Consequences of Hormonal Interactions between Opposite-sex Twin Fetuses

In human opposite-sex twins, certain phenotypic traits of the female are affected negatively by testosterone transfer from the male, while the male may or may not be affected by the female in utero. However, no study was carried out to uncover the epigenetic basis of these effects. Here, we generated DNA methylation data from 54 newborn twins and histone modification data from 14 newborn twins, including female-female (FF), female-male (FM), and male-male (MM) newborn twins, to exclude the effects of postnatal environment and socialization, and investigated the epigenetic consequences of prenatal interactions between female and male gonadal hormones. We found that FM-Fs (female in FM twins) were distinguishable from FF twins by their DNA methylome, as were FM-Ms (male in FM twins) from MM twins. The correlation between genome-wide DNA methylation of females and males showed that FM-Fs, but not FFs, were closer to males from FM-Ms and MMs. Interestingly, the DNA methylomic differences between FM-Fs and FFs, but not those between FM-Ms and MMs, were linked to cognition and the nervous system. Meanwhile, FM-Ms and MMs, but not FM-Fs and FFs, displayed differential histone modification of H3K4me3, which were linked to immune responses. These findings provide epigenetic evidence for the twin testosterone transfer hypothesis and explain how prenatal hormone exposure is linked to reported and novel traits of childhood and adult through the epigenome in opposite-sex twins. Author SummaryPrenatal exposure to testosterone may affect physiological, cognitive, and behavioral traits in females with male co-twins, while the males in opposite-sex twins present weak and inconsistent influences. In this study, we systematically investigated the hormonal interactions between opposite-sex twins in newborns from epigenetics including DNA methylation and histone modifications. We show that DNA methylome in FM-Fs (female in FM twins) was different from FF twins and their DNA methylomic differences were associated with cognition and the nervous system. We also suggest that FM-Ms (male in FM twins) were distinguishable from MM twins by their DNA methylome and FM-Ms versus MMs displayed differential histone modification of H3K4me3, which were linked to immune responses. Our study provides insight into the epigenetic explanation for hormonal influences between opposite-sex fetuses.

developmental biology↗

bioRxiv2020

OGP: A Repository of Experimentally Characterized O-Glycoproteins to Facilitate Studies on O-Glycosylation

Numerous studies on cancer, biopharmaceuticals, and clinical trials have necessitated comprehensive and precise analysis of protein O-glycosylation. However, the lack of updated and convenient databases deters the storage and utilization of emerging O-glycoprotein data. To resolve this issue, an O-glycoprotein repository named OGP was established in this work. It was constructed with a collection of O-glycoprotein data from different sources. OGP contains 9354 O-glycosylation sites and 11,633 site-specific O-glycans mapping to 2133 O-glycoproteins, and it is the largest O-glycoprotein repository thus far. Based on the recorded O-glycosites, an O-glycosylation site prediction tool was developed. Moreover, an OGP-backed website is already available (http://www.oglyp.org/). The website comprises four specially designed and user-friendly modules: Statistic Analysis, Database Search, Site Prediction, and Data Submit. The first version of OGP repository and the website allow users to obtain vast O-glycoprotein related information, such as protein accession numbers, glycopeptides, site-specific glycan structures, experimental methods, and potential glycosylation sites. O-glycosylation data mining can be performed efficiently on this website, which can greatly facilitates O-glycosylation studies.

bioinformatics↗

bioRxiv2019

Rapid disruption of the cortical microcirculation after mild traumatic brain injury

Traumatic brain injury (TBI) is a major source of cognitive deficits affecting millions annually. The bulk of human injuries are mild, causing little or no macroscopic damage to neural tissue, yet can still lead to long-term neuropathology manifesting months or years later. Although the cellular stressors that ultimately lead to chronic pathology are poorly defined, one notable candidate is metabolic stress due to reduced cerebral blood flow (CBF), which is common to many forms of TBI. Here we used high-resolution in vivo intracranial imaging in a rodent injury model to characterize deficits in the cortical microcirculation during both acute and chronic phases after mild TBI. We found that CBF dropped precipitously during immediate post-injury periods, decreasing to less than half of baseline levels within minutes and remaining suppressed for 1.5-2 hours. Repeated time-lapse imaging of the cortical microvasculature revealed further striking flow deficits in the capillary network, where 18% of vessels were completely occluded for extended periods after injury, and an additional >50% showed substantial stoppages. Decreased CBF was paralleled by extensive vasoconstriction that is likely to contribute to loss of flow. Our data indicate a major role for vascular dysfunction in even mild forms of TBI, and suggest that acute post-injury periods may be key therapeutic windows for interventions that restore flow and mitigate metabolic stress.

neuroscience↗

bioRxiv2019

Enhancer-promoter association determines Sox2 transcription regulation in mouse pluripotent cells

Distal enhancer-promoter associations are essential for transcription control and emerging as a common epigenetic way to determine gene expression in eukaryotes. However, it remains as an uncultivated land on how their diversity influences gene transcription during development. In this study, we select three defined Sox2 associated enhancers (E1, E2 and E3), representing different distal interaction categories, to further explore their biological effects. We construct three enhancer-knockout cells via CRISPR/Cas9 system in mouse embryonic stem cells. Results show that these associations carry out various biological features. Embryonic stem cell specific association (E1) speeds up cell cycle and involves in cardiac development, which has been validated in vivo. In contrast, the indirect one (E2) restrains nerve differentiation and has potential effect on lipid metabolism. The common one (E3) promotes nerve differentiation and inhibits oxidation-reduction process. Together, these different associations determine Sox2 transcription and function specificity in mouse embryonic stem cells. Our study will enable a way for exploring miscellaneous spatiotemporal gene transcription control and advancing quantitative knowledge by utilizing three-dimensional genomic information.\n\nSummary statementSox2 transcription is complicated in mouse embryonic stem cells. It involves in heavily enhancer-promoter associations, which might make it a suitable model for phase-separation study. To decompose this cooperative regulation, diverse interactions are investigated. The biological effects have been explored in multiple perspectives. This may represent a quantitative way to explore and a potential new strategy to transcription control study.

molecular biology↗

bioRxiv2018

Deletion of YAP/TAZ in mouse neocortex impaired the proliferation and differentiation ability of neural progenitor cells

YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are downstream effectors of the Hippo pathway, they activate the expression of transcriptional targets that promote cell growth, cell proliferation, and prevent apoptosis. Here I examined the function of YAP/TAZ in mouse neocortex development through conditional deletion of Yap and Taz by Emx1-Cre. Loss of YAP/TAZ cause the hydrocephalus after birth, leads to aberrant development and dilated ventricle in adult stage, this phenotype can be detected as early as P0. YAP/TAZ are expressed in Sox2+ neural progenitor cells, when YAP/TAZ are deleted, the neuroepithelial cell junctions are disrupted; the numbers of Sox2+ cell and Tbr2+ cell are reduced and the ratio of tbr2/Sox2 is also reduced at E15.5. Results of cell cycle analyzing experiments display YAP/TAZ deletion increased the cell cycle exit. The improperly increased expression of Tuj1+ in progenitor cells in the YAP/TAZ deleted cortex indicates the premature of Sox2+ progenitor cells. Together, our results reveal that YAP/TAZ deletion changed the polarity of neuroepithelial cells, and increased the cell cycle exit, reduced the differentiation of Sox2+ cells into Tbr2+ cells through promoting the premature of Tuj1+ cells. These results define the functions of YAP/TAZ in keeping the cell polarity neural progenitors and ensuring their proliferation and differentiation, and also reveal the roles of YAP/TAZ in developing cortex.

neuroscience↗

bioRxiv2017

Investigation of the role of a macromolecular complex of CFTR-NHERF2-LPA2 in the fluid hemostasis and inflammatory responses in intestinal epithelial cells

CFTR is a cAMP-regulated chloride channel located in the apical surface of intestinal epithelial cells; where it forms a macromolecular complex with NHERF2 and LPA2. CFTR has been shown to play a role in the pathogenies of several types of secretory diarrheas. Inflammatory bowel disease (IBD) is a chronic condition of intestine characterized by severe inflammation and mucosal destruction, genetic analysis has shown that LPA contribute to IBD and patients of cystic fibrosis also display the phenotype of diarrhea. The purpose of this study is to investigate if this complex plays a role in the inflammatory responses of intestinal epithelium.\n\nWe then explored the role of this complex in maintaining the integrity of tight junction and inflammatory responses in these cells. In vitro assays show that inhibiting CFTR or LPA2 in the intestinal epithelial cell could disrupt the epithelial cell junction, and reduce the TER of intestinal epithelial cells in both mouse and human cell line. EUSA assay show that intriguing LPA2 through LPS or LPA can increase the secretion of IL-8, while inhibiting or SiRNA knockdown of LPA2 can decrease the secretion of IL-8 in mouse or human intestinal epithelial cells. The CFTR inhibitor can reduce the IL-8 secretion in both mouse and human cell line, the deletion of CFTR in mouse intestine does not affect the IL-8 level, but the knockdown of CFTR in human cell line reduced the IL-8 protein level. The deletion of CFTR in human also reduced the IL-8 mRNA level. This indicates the CFTR-LPA complex is necessary for the expression of IL-8.

pathology↗

bioRxiv2017

Dlic1 deletion impaired cerebellar development in mouse

The cerebellum is an important model system to study Central Nervous System, it has a striking morphology consisting of folia separated by fissures of different lengths, and the molecules controlling the process of cerebellar development have been unclear. In this study, we report an unrecognized contribution of Dlic1 to the postnatal development of murine cerebellum. Dlic1 encodes a light intermediate chain of cytoplasmic dynein 1, it is a subunit unique to the cytoplasmic form of dynein, and how it contributes to dynein function is not fully understood. Our data show that Dlic1 deletion leads to impaired cerebellar development, foliation and fissuration, the volume of the cerebellum was evidently reduced. Consistent with the histological defects, Dlic1 knockout mice show defective motor coordination, this strongly indicates the fundamental role of Dlic1 in cerebellar development and function. Purkinje cells are located within the cerebellum and form synapses with granule cells. In Dlic1-/- mice, Purkinje cells display reduced dendritic complexity and the distribution of dynein in Purkinje cell layer is changed. We also found that Dlic1 deletion reduced the protein levels of dynein subunits and leads to the defective assembling of dynein subunits. These data indicate that Dlic1 may affect cerebellar development through affecting the normal function of dynein.\n\nAbbreviations

neuroscience↗