Biology subjects

Liang, X.

Publications and source records attributed to Liang, X..

At least 181 records · Page 10Linked to original sources

bioRxiv2020

Endophilin A1 promotes Actin Polymerization in response to Ca2+/calmodulin to Initiate Structural Plasticity of Dendritic Spines

Dendritic spines of excitatory neurons undergo activity-dependent structural and functional plasticity, which are cellular correlates of learning and memory. However, mechanisms underlying the rapid morphological changes immediately after NMDAR-mediated Ca2+ influx into spines remain poorly understood. Here we report that endophilin A1, a neuronal N-BAR protein, orchestrates membrane dynamics with actin polymerization to initiate spine enlargement in the induction phase of long-term potentiation (LTP). Upon LTP induction, Ca2+/calmodulin enhances its binding to both membrane and p140Cap, a cytoskeleton regulator. As a result, endophilin A1 rapidly associates with the relaxed plasma membrane and promotes actin polymerization, leading to acute expansion of spine head. Moreover, not only the p140Cap-binding, but also calmodulin- and membrane-binding capacities of endophilin A1 are required for LTP and long-term memory. Thus, endophilin A1 functions as calmodulin effector to drive spine enlargement in response to Ca2+ influx in the initial phase of structural plasticity.

cell biology↗

bioRxiv2020

Microvascular Injury in Mild Traumatic Brain Injury Accelerates Alzheimer-like Pathogenesis in Mice

IntroductionTraumatic brain injury (TBI) is considered as the most robust environmental risk factor for Alzheimers disease (AD). Besides direct neuronal injury and neuroinflammation, vascular impairment is also a hallmark event of the pathological cascade after TBI. However, the vascular connection between TBI and subsequent AD pathogenesis remains underexplored. MethodsWe established a closed-head mild TBI (mTBI) model in mice with controlled cortical impact, and examined the time courses of microvascular injury, blood-brain barrier (BBB) dysfunction, gliosis and motor function impairment in wild type C57BL/6 mice. We also determined the brain clearance of {beta}-amyloid, as well as amyloid pathology and cognitive functions after mTBI in the 5xFAD mouse model of AD. ResultsmTBI induced microvascular injury with BBB breakdown, pericyte loss and cerebral blood flow reduction in mice, which preceded gliosis. mTBI also impaired brain amyloid clearance via the vascular pathways. More importantly, mTBI accelerated amyloid pathology and cognitive impairment in the 5xFAD mice. DiscussionOur data demonstrated that microvascular injury plays a key role in the pathogenesis of AD after mTBI. Therefore, restoring vascular functions might be beneficial for patients with mTBI, and potentially reduce the risk of developing AD.

neuroscience↗

bioRxiv2020

Comparative genomic analysis revealed specific mutation pattern between human coronavirus SARS-CoV-2 and Bat-SARSr-CoV RaTG13

The novel coronavirus SARS-CoV-2 (2019-nCoV) is a member of the family coronaviridae and contains a single-stranded RNA genome with positive-polarity. To reveal the evolution mechanism of SARS-CoV-2 genome, we performed comprehensive genomic analysis with newly sequenced SARS-CoV-2 strains and 20 closely related coronavirus strains. Among 98 nucleotide mutations at 93 sites of the genome among different SARS-CoV-2 strains, 58 of them caused amino acid change, indicating a result of neutral evolution. However, the ratio of nucleotide substitutions to amino acid substitutions of spike gene (9.07) between SARS-CoV-2 WIV04 and Bat-SARSr-CoV RaTG13 was extensively higher than those from comparisons between other coronaviruses (range 1.29 - 4.81). The elevated synonymous mutations between SARS-CoV-2 and RaTG13, suggesting they underwent stronger purifying selection. Moreover, their nucleotide substitutions are enriched with T:C transition, which is consistent with the mutation signature caused by deactivity of RNA 3-to-5 exoribonuclease (ExoN). The codon usage was similar between SARS-CoV-2 and other strains in beta-coronavirus lineage B, suggesting it had small impact on the mutation pattern. In comparison of SARS-CoV-2 WIV04 with Bat-SARSr-CoV RaTG13, the ratios of non-synonymous to synonymous substitution rates (dN/dS) was the lowest among all performed comparisons, reconfirming the evolution of SARS-CoV-2 under stringent selective pressure. Moreover, some sites of spike protein might be subjected to positive selection. Therefore, our results will help understanding the evolutionary mechanisms contribute to viral pathogenicity and its adaptation with hosts.

genomics↗

bioRxiv2020

DPHL: A pan-human protein mass spectrometry library for robust biomarker discovery using Data-Independent Acquisition and Parallel Reaction Monitoring

To answer the increasing need for detecting and validating protein biomarkers in clinical specimens, proteomic techniques are required that support the fast, reproducible and quantitative analysis of large clinical sample cohorts. Targeted mass spectrometry techniques, specifically SRM, PRM and the massively parallel SWATH/DIA technique have emerged as a powerful method for biomarker research. For optimal performance, they require prior knowledge about the fragment ion spectra of targeted peptides. In this report, we describe a mass spectrometric (MS) pipeline and spectral resource to support data-independent acquisition (DIA) and parallel reaction monitoring (PRM) based biomarker studies. To build the spectral resource we integrated common open-source MS computational tools to assemble an open source computational workflow based on Docker. It was then applied to generate a comprehensive DIA pan-human library (DPHL) from 1,096 data dependent acquisition (DDA) MS raw files, and it comprises 242,476 unique peptide sequences from 14,782 protein groups and 10,943 SwissProt-annotated proteins expressed in 16 types of cancer samples. In particular, tissue specimens from patients with prostate cancer, cervical cancer, colorectal cancer, hepatocellular carcinoma, gastric cancer, lung adenocarcinoma, squamous cell lung carcinoma, diseased thyroid, glioblastoma multiforme, sarcoma and diffuse large B-cell lymphoma (DLBCL), as well as plasma samples from a range of hematologic malignancies were collected from multiple clinics in China, the Netherlands and Singapore and included in the resource. This extensive spectral resource was then applied to a prostate cancer cohort of 17 patients, consisting of 8 patients with prostate cancer (PCa) and 9 with benign prostate hyperplasia (BPH), respectively. Data analysis of DIA data from these samples identified differential expressions of FASN, TPP1 and SPON2 in prostate tumors. Thereafter, PRM validation was applied to a larger PCa cohort of 57 patients and the differential expressions of FASN, TPP1 and SPON2 in prostate tumors were validated. As a second application, the DPHL spectral resource was applied to a patient cohort consisting of samples from 19 DLBCL patients and 18 healthy individuals. Differential expressions of CRP, CD44 and SAA1 between DLBCL cases and healthy controls were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supported that DIA-PRM MS pipeline enables robust protein biomarker discoveries.

bioinformatics↗

bioRxiv2020

A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission

The ESCRT complexes drive membrane scission in HIV-1 release, autophagosome closure, MVB biogenesis, cytokinesis, and other cell processes. ESCRT-I is the most upstream complex and bridges the system to HIV-1 Gag in virus release. The crystal structure of the headpiece of human ESCRT-I comprising TSG101:VPS28:VPS37B:MVB12A was determined, revealing an ESCRT-I helical assembly with a 12 molecule repeat. Electron microscopy confirmed that ESCRT-I subcomplexes form helical filaments in solution. Mutation of VPS28 helical interface residues blocks filament formation in vitro and autophagosome closure and HIV-1 release in human cells. Coarse grained simulations of ESCRT assembly at HIV-1 budding sites suggest that formation of a 12-membered ring of ESCRT-I molecules is a geometry-dependent checkpoint during late stages of Gag assembly and HIV-1 budding, and templates ESCRT-III assembly for membrane scission. These data show that ESCRT-I is not merely a bridging adaptor, but has an essential scaffolding and mechanical role in its own right.

biophysics↗

bioRxiv2020

New mathematical modelling tools for co-culture experiments: when do we need to explicitly account for signalling molecules?

Mathematical models are often applied to describe cell migration regulated by diffusible signalling molecules. A typical feature of these models is that the spatial and temporal distribution of the signalling molecule density is reported by solving a reaction-diffusion equation. However, the spatial and temporal distributions of such signalling molecules are not often reported or observed experimentally. This leads to a mismatch between the amount of experimental data available and the complexity of the mathematical model used to simulate the experiment. To address this mismatch, we develop a discrete model of cell migration that can be used to describe a new suite of co-culture cell migration assays involving two interacting subpopulations of cells. In this model, the migration of cells from one subpopulation is regulated by the presence of signalling molecules that are secreted by the other subpopulation of cells. The spatial and temporal distribution of the signalling molecules is governed by a discrete conservation statement that is related to a reaction-diffusion equation. We simplify the model by invoking a steady state assumption for the diffusible molecules, leading to a reduced discrete model allowing us to describe how one subpopulation of cells stimulates the migration of the other subpopulation of cells without explicitly dealing with the diffusible molecules. We provide additional mathematical insight into these two stochastic models by deriving continuum limit partial differential equation descriptions of both models. To understand the conditions under which the reduced model is a good approximation of the full model, we apply both models to mimic a set of novel co-culture assays and we systematically explore how well the reduced model approximates the full model as a function of the model parameters.

biophysics↗

bioRxiv2019

Advanced Whole Genome Sequencing Using a Complete PCR-free Massively Parallel Sequencing (MPS) Workflow

BackgroundSystematic errors can be introduced from DNA amplification during massively parallel sequencing (MPS) library preparation and sequencing array formation. Polymerase chain reaction (PCR)-free genomic library preparation methods were previously shown to improve whole genome sequencing (WGS) quality on the Illumina platform, especially in calling insertions and deletions (InDels). We hypothesized that substantial InDel errors continue to be introduced by the remaining PCR step of DNA cluster generation. In addition to library preparation and sequencing, data analysis methods are also important for the accuracy of the output data.In recent years, several machine learning variant calling pipelines have emerged, which can correct the systematic errors from MPS and improve the data performance of variant calling. ResultsHere, PCR-free libraries were sequenced on the PCR-free DNBSEQ arrays from MGI Tech Co., Ltd. (referred to as MGI) to accomplish the first true PCR-free WGS which the whole process is truly not only PCR-free during library preparation but also PCR-free during sequencing. We demonstrated that PCR-based WGS libraries have significantly (about 5 times) more InDel errors than PCR-free libraries.Furthermore, PCR-free WGS libraries sequenced on the PCR-free DNBSEQ platform have up to 55% less InDel errors compared to the NovaSeq platform, confirming that DNA clusters contain PCR-generated errors.In addition, low coverage bias and less than 1% read duplication rate was reproducibly obtained in DNBSEQ PCR-free using either ultrasonic or enzymatic DNA fragmentation MGI kits combined with MGISEQ-2000. Meanwhile, variant calling performance (single-nucleotide polymorphisms (SNPs) F-score>99.94%, InDels F-score>99.6%) exceeded widely accepted standards using machine learning (ML) methods (DeepVariant or DNAscope). ConclusionsEnabled by the new PCR-free library preparation kits, ultra high-thoughput PCR-free sequencers and ML-based variant calling, true PCR-free DNBSEQ WGS provides a powerful solution for improving WGS accuracy while reducing cost and analysis time, thus facilitating future precision medicine, cohort studies, and large population genome projects.

genomics↗

bioRxiv2019

Identification of regulators of poly-ADP-ribose polymerase (PARP) inhibitor response through complementary CRISPR knockout and activation screens

Inhibitors of poly-ADP-ribose polymerase 1 (PARPi) are highly effective in killing cells deficient in the homologous recombination (HR) DNA repair pathway, such as those lacking BRCA2. In light of this, PARPi have been utilized in recent years to treat BRCA2-mutant tumors, with many patients deriving impressive clinical benefit. However, positive response to PARPi is not universal, even among patients with HR-deficient tumors. Here, we present the results of three genome-wide CRISPR knockout and activation screens which provide an unbiased look at genetic determinants of PARPi response in wildtype or BRCA2-knockout cells. Strikingly, we reveal that depletion of the histone acetyltransferase TIP60, a top hit from our screens, robustly reverses the PARPi sensitivity caused by BRCA2 deficiency. Mechanistically, we show that TIP60 depletion rewires double strand break repair in BRCA2-deficient cells by promoting 53BP1 binding to double strand breaks to suppress end resection. Our work provides a comprehensive set of putative biomarkers that serve to better understand and predict PARPi response, and identifies a novel pathway of PARPi resistance in BRCA2-deficient cells.

molecular biology↗

bioRxiv2019

Comparison of the Gut Microbiota Composition Between Captive and Wild Roe Deer

In this paper, 16S-rRNA gene Illumina HiSeq sequencing was used to analyze the structural diversity of captive and wild roe deer gut flora. The results show that the microbial diversity in the feces of wild roe deer is higher than in that of captive roe deer. Both roe deer have similar flora at the phylum level, but the main genus has significant differences. The microbial group that plays an important role in captive roe deer is Bacteroidetes; in wild roe deer it is Firmicutes. This difference is mainly due to the differences in living environment, diet, and physiological functions of the two groups. In conclusion, our study makes people have a better understanding of the intestinal flora of roe deer. By comparing the intestinal microbial structure differences between captive and wild roe deer, it provides theoretical basis for people to raise captive roe deer and provides reference for the protection of wild roe deer.\n\nIMPORTANCEMany studies have shown that large and complex microbes in the gut of humans and non-human animals, intestinal microbes are thought to co-evolve with the host, help the host acquire nutrients, regulate immunity and to help maintain host homeostasis. The roe deer (Capreolus spp.) is a ruminant. Wild roe deer are listed on the List of Terrestrial Wild Animals Protected by the State or Have Important Economic and Scientific Values, wild roe deer is also a Chinese national protected animal under second class protection. However, current research on the gut microbiota of roe deer has not been reported.

microbiology↗

bioRxiv2019

DNA Methylation Signature on Phosphatidylethanol, not Self-Reported Alcohol Consumption, Predicts Hazardous Alcohol Consumption in Two Distinct Populations

The process of diagnosing hazardous alcohol drinking (HAD) is based on self-reported data and is thereby vulnerable to bias. There has been an interest in developing epigenetic biomarkers for HAD that might complement clinical assessment. Because alcohol consumption has been previously linked to DNA methylation (DNAm), here, we aimed to select DNAm signatures in blood to predict HAD from two demographically and clinically distinct populations (Ntotal=1,549). We first separately conducted an epigenome-wide association study (EWAS) for phosphatidylethanol (PEth), an objective measure of alcohol consumption, and for self-reported alcohol consumption in Cohort 1. We identified 102 PEth-associated CpGs, including 32 CpGs previously associated with alcohol consumption or alcohol use disorders. In contrast, no CpG reached epigenome-wide significance on self-reported alcohol consumption. Using a machine learning approach, two subsets of CpGs from EWAS on PEth and on self-reported alcohol consumption from Cohort 1 were separately tested for the prediction of HAD in Cohort 2. We found that a subset of 130 CpGs selected from the EWAS on PEth showed an excellent prediction of HAD with area under the ROC curve (AUC) of 91.31% in training set and 70.65% in validation set of Cohort 2. However, CpGs preselected from the EWAS on self-reported alcohol consumption showed a poor prediction of HAD with AUC 75.18% in the training set and 57.60% in the validation set. Our results demonstrate that an objective measure for alcohol consumption is a more informative phenotype than self-reported data for revealing epigenetic mechanism. The PEth-associated DNAm signature in blood is a robust biomarker for alcohol consumption.

bioinformatics↗

bioRxiv2019

High-depth resequencing reveals hybrid population and insecticide resistance characteristics of fall armyworm (Spodoptera frugiperda) invading China

The rapid wide-scale spread of fall armyworm (Spodoptera frugiperda) has caused serious crop losses globally. However, differences in the genetic background of subpopulations and the mechanisms of rapid adaptation behind the invasion are still not well understood. Here we report a 393.25-M chromosome-level genome assembly of fall armyworm with scaffold N50 of 13.3 M consisting of 23281 annotated protein-coding genes. Genome-wide resequencing of 105 samples from 16 provinces in China revealed that the fall armyworm population comprises a complex inter-strain hybrid, mainly with the corn-strain genetic background and less of the rice-strain genetic background, which highlights the inaccuracy of strain identification using mitochondrial or Tpi genes. An analysis of genes related to pesticide- and Bt-resistance showed that the risk of fall armyworm developing resistance to conventional pesticides is very high, while remaining currently susceptible to Bt toxins. Laboratory bioassay results showed that insects invading China carry resistance to organophosphate and pyrethroid pesticides, but are sensitive to genetically modified maize expressing Cry1Ab in field experiments. Additionally, we found that two mitochondrial fragments are inserted into the nuclear genome, and the insertion event occurred after the differentiation of the two strains. This study represents a valuable advancement toward the analysis of genetic differences among subpopulations and improving management strategies for fall armyworm.

genomics↗

bioRxiv2019

LARP7 is a BRCA1 ubiquitinase substrate and regulates genome stability and tumorigenesis

Attenuated DNA repair leads to genomic instability and tumorigenesis. BRCA1/BARD1 are the best known tumor suppressors that promote homology recombination (HR) and arrest cell cycle at G2/M checkpoint. As E3 ubiquitin ligases, their ubiquitinase activity has been known to involve in the HR and tumor suppression, but the mechanism remains ambiguous. Here, we demonstrated upon genotoxic stress, BRCA1 together with BARD1 catalyzed the K48 ployubiquitination on LARP7, a 7SK RNA binding protein known to control RNAPII pausing, and thereby degraded it through 26S ubiquitin-proteasome pathway. Depleting LARP7 suppressed the expression of CDK1 complex, arrested cell at G2/M DNA damage checkpoint and reduced BRCA2 phosphorylation which thereby facilitated RAD51 recruitment to damaged DNA to enhance HR. Importantly, LARP7 depletion observed in breast patients lead to the chemoradiotherapy resistance both in vitro and in vivo. Together, this study unveils a mechanism by which BRCA1/BARD1 utilizes their E3 ligase activity to control HR and cell cycle, and highlights LARP7 as a potential target for cancer prevention and therapy.\n\nHighlightsO_LIDNA damage response downregulates LARP7 through BRCA1/BARD1\nC_LIO_LIBRCA1/BARD1 catalyzes the K48 polyubiquitination on LARP7\nC_LIO_LILARP7 promotes G2/M cell cycle transition and tumorigenesis via CDK1 complex\nC_LIO_LILARP7 disputes homology-directed repair that leads to tumor therapy resistance\nC_LI

molecular biology↗

bioRxiv2019

Prophage induction mediated by quorum sensing signals alters soil bacterial community structure

Recent findings have revealed a role for bacterial quorum sensing communication in bacteriophage (phage) reproduction decisions. However quorum sensing based phage-host interactions remain largely unknown, with the mechanistic details revealed for only a few phage-host pairs and a dearth of information available at the microbial community level. Here we report on the specific action of individual quorum-sensing signals (acyl-homoserine lactones; AHLs varying in acyl-chain length from four to 14 carbon atoms) on prophage induction in soil microbial communities. AHL treatment significantly decreased the bacterial diversity (Shannon Index) but did not significantly impact species richness. Exposure to short chain-length AHLs resulted in a decrease in the abundance of different taxa than exposure to higher molecular weight AHLs. Each AHL targeted a different subset of bacterial taxa. Our observations demonstrate that individual AHLs trigger prophage induction in different bacterial taxa leading to changes in microbial community structure.

microbiology↗

bioRxiv2019

Placental Editome Profiling Reveals Widespread RNA-Editing Dysregulation in Preeclampsia

Dysregulated RNA editing is well documented in several diseases such as cancer. The extent to which RNA editing might be involved in diseases originated in the placenta remains unknown, because RNA editing has rarely been studied in the placenta. Here, we have systematically profiled RNA editome on the placentae from 9 patients with early-onset severe preeclampsia (EOSPE) and 32 normal subjects, and a widespread RNA editing dysregulation in EOSPE has been identified. The mis-edited gene set is enriched with known preeclampsia-associated genes and differentially expressed genes in EOSPE. The \"RNA editing events\" at two microRNA binding sites in 3-UTR of the LEP mRNA were generated, which could lead to increased expression level of LEP in trophoblast cells. Upregulation of LEP were also observed in the placentae of PE patients. These results suggest that widespread placental RNA editing may be involved in placental development and dysregulation of RNA editing in the placenta may contribute to the pathogenesis of preeclampsia.

genomics↗

bioRxiv2019

Detection and characterization of copy number variants based on whole-genome sequencing by MGI platforms

BackgroundNext-generation sequence (NGS) has rapidly developed in past years which makes whole-genome sequencing (WGS) becoming a more cost- and time-efficient choice in wide range of biological researches. We usually focus on some variant detection via WGS data, such as detection of single nucleotide polymorphism (SNP), insertion and deletion (Indel) and copy number variant (CNV), which playing an important role in many human diseases. However, the feasibility of CNV detection based on WGS by DNBSEQ platforms was unclear. We systematically analysed the genome-wide CNV detection power of DNBSEQ platforms and Illumina platforms on NA12878 with five commonly used tools, respectively.\n\nResultsDNBSEQ platforms showed stable ability to detect slighter more CNVs on genome-wide (average 1.24-fold than Illumina platforms). Then, CNVs based on DNBSEQ platforms and Illumina platforms were evaluated with two public benchmarks of NA12878, respectively. DNBSEQ and Illumina platforms showed similar sensitivities and precisions on both two benchmarks. Further, the difference between tools for CNV detection was analyzed, and indicated the selection of tool for CNV detection could affected the CNV performance, such as count, distribution, sensitivity and precision.\n\nConclusionThe major contribution of this paper is providing a comprehensive guide for CNV detection based on WGS by DNBSEQ platforms for the first time.

bioinformatics↗

bioRxiv2019

An integrated Asian human SNV and indel benchmark combining multiple sequencing methods

Precision medicine of human requires an accurate and complete reference variant benchmark for different populations. A human standard cell line of NA12878 provides a good reference for part of the human populations, but it is still lack of a fine reference standard sample and variant benchmark for the Asians. Here, we constructed a stabilized cell line of a Chinese Han volunteer. We received about 4.16T clean data of the sample using eight sequencing strategies in different laboratories, including two BGI regular NGS platforms, three Illumina regular NGS platforms, two linked-read libraries, and PacBio CCS model. The sequencing depth and reference coverage of eight sequencing strategies have reached the saturation. We detected small variants of SNPs and Indels using the eight data sets and obtained eight variant sets by performing a series of strictly quality control. Finally, we got 3.35M SNPs and 349K indels supported by all of sequencing data, which could be considered as a high confidence standard small variant sets for the studies. Besides, we also detected 5,913 high quality SNPs located in the high homologous regions supported by both linked-reads and CCS data benefited by their long-range information, while these regions are recalcitrant to regular NGS data due to the limited mappability and read length. We compared the later SNPs against the public databases and 969 sites of them were novel SNPs, indicating these SNPs provide a vital complement for the variant database. Moreover, we also phased more than 99% heterozygous SNPs also supported by linked-reads and CCS data. This work provided an integrated Asians SNV and indel benchmark for the further basic studies and precision medicine.

genomics↗

bioRxiv2019

Systematic search for schizophrenia pathways sensitive to perturbation by immune activation

Immune activation has been recently found to play a large part in the development of schizophrenia, but the underlying mechanism remains largely unknown. Here, we report the construction of a high-quality protein interaction network for schizophrenia (SCZ Network) using a \"neighborhood walking\" approach to searching across human interactome network for disease-related neighborhoods. The spatiotemporal expression pattern of the immune genes in the SCZ Network demonstrates that this disease network is sensitive to the perturbation of immune activation during mid- to late fetal development and adolescence. The immune genes in the network are involved in pathways regulating the formation, structure and function of synapses and neural connections. Using single-cell transcriptome sequencing on the brains of immune-activated mice, we found that immune activation disturbed the SCZ network in the major brain cell types and the dysregulated pathways were also involved in synapse regulation, demonstrating that our \"neighborhood walking\" approach enables biological discovery in complex disorders.

systems biology↗

bioRxiv2019

Essential role of Bone morphogenetic protein 15 in porcine ovarian and follicular development and ovulation

Bone morphogenetic protein 15 (BMP15) is a multifunctional oocyte-specific secreted factor. It controls female fertility and follicular development in both species-specific and dosage-sensitive manners. Previous studies found that BMP15 played a critical role on follicular development and ovulation rate of mono-ovulatory mammalian species, but has minimal impact on poly-ovulatory mice. However, whether this is true in non-rodent poly-ovulatory species need to be validated. To investigate this question, we generated a BMP15 knockdown pig model. We found that BMP15 knockdown gilts showed markedly reduced fertility accompanied with phenotype of dysplastic ovaries containing significantly declined number of follicles, increased number of abnormal follicles, and abnormally enlarged antral follicles resulting in disordered ovulation. Molecular and transcriptome analysis revealed that knockdown of BMP15 significantly suppressed cell proliferation, differentiation, Fshr expression, leading to premature luteinization and reduced estradiol production in GCs, and simultaneously decreased the quality and meiotic maturation of oocyte. Our results provide in vivo evidences for the essential role of BMP15 in porcine ovarian and follicular development, and new insight into the complicated regulatory function of BMP15 in female fertility of poly-ovulatory species.

developmental biology↗