Biology subjects

Hu, S.

Publications and source records attributed to Hu, S..

At least 181 records · Page 10Linked to original sources

bioRxiv2020

Gene polymorphism associated with Angiotensinogen(M235T), Endothelial lipase (584C/T) and susceptibility to coronary artery disease: A meta-analysis

ObjectiveTo explore the association between the variant M235 locus of angiotensinogen (AGT) gene, 584C/T locus of Endothelial lipase (EL) gene, and coronary artery disease (CAD) by meta-analysis. MethodsThe case-control studies on the association between AGT/EL gene polymorphism and CAD were collected through searching PubMed, EMbase, Web of Science, CNKI and Wanfang database up to March 1, 2020. Stata 15.0 software was used for analysis. ResultsA total of 29 articles met the inclusion criteria. After analyzing, it was found that the M235T polymorphism of AGT gene was associated with the occurrence of CAD. In the allele model (T vs. M), OR=1.38 (P < 0.05). In other heredity, there was also statistically significant. Subgroup analysis indicated that except the heterozygous genetic model of the Chinese population, other genetic models of the Caucasian and Chinese population were also statistically significant. The 584C/T polymorphism of EL gene was associated with the occurrence of CAD, with OR=0.83 (P < 0.05) in the allele model (T vs. C) and OR=0.80 (P < 0.05) in the dominant gene model. Also, in the allele model of Caucasian subgroup, OR=0.83 (P < 0.05), while in Asian subgroup, there was no statistically significant genetic model. ConclusionAGT M235 and EL 584C/T polymorphisms are associated with CAD susceptibility. The genotype TT, TC or allele T of AGT M235T and genotype CC or allele C of EL 584C/T might be the genetic risk factors for the development of CAD.

molecular biology↗

bioRxiv2020

LINCS gene expression signatures analysis revealed bosutinib as a radiosensitizer of breast cancer cells by targeting eIF4G1

Radioresistance represents the predominant cause for radiotherapy failure and disease progression, resulting in increased breast cancer mortality. Through gene expression signatures analyses of Library of Integrated Network-Based Cellular Signatures (LINCS) and Gene Expression Omnibus (GEO), the present study aimed to identify potential candidate radiosensitizers from known drugs systematically. The similarity of integrated gene expression signatures between irradiated eIF4G1-silenced breast cancer cells and known drugs was measured by enrichment scores. Drugs with positive enrichment scores were selected as potential radiosensitizers. The radiosensitizing effects of the candidate radiosensitizers were analyzed in breast cancer cells (MCF-7, MX-1, and MDA-MB-231) by CCK-8 assays and colony-forming capability after exposure to ionizing radiation. Cell apoptosis was detected by flow cytometry. Expressions of eIF4G1 and a series of DNA damage response proteins were analyzed by Western blot assays. Bosutinib was proposed to be a promising radiosensitizer as its administration markedly reduced the dosages of both the drug and ionizing radiation and was associated with fewer adverse drug reactions. The combined treatment with ionizing radiation and bosutinib significantly increased the cells killing potency in all three cell lines as compared to ionizing radiation or bosutinib alone. MX-1 cells were revealed to be the most sensitive to both ionizing radiation and bosutinib among the three cell lines. Bosutinib noticeably downregulated the expression of eIF4G1 in a dose-dependent manner and also reduced the expression of DNA damage response proteins (including ATM, XRCC4, ATRIP, and GADD45a). Moreover, eIF4G1 could be a key target of bosutinib through which it regulates DNA damage induced by ionizing radiation. Thus, taken together, bosutinib may serve as a potential candidate radiosensitizer for breast cancer therapy.

cancer biology↗

bioRxiv2020

Structure-Based Design, Synthesis and Biological Evaluation of Peptidomimetic Aldehydes as a Novel Series of Antiviral Drug Candidates Targeting the SARS-CoV-2 Main Protease

SARS-CoV-2 is the etiological agent responsible for the COVID-19 outbreak in Wuhan. Specific antiviral drug are urgently needed to treat COVID-19 infections. The main protease (Mpro) of SARS-CoV-2 is a key CoV enzyme that plays a pivotal role in mediating viral replication and transcription, which makes it an attractive drug target. In an effort to rapidly discover lead compounds targeting Mpro, two compounds (11a and 11b) were designed and synthesized, both of which exhibited excellent inhibitory activity with an IC50 value of 0.05 M and 0.04 M respectively. Significantly, both compounds exhibited potent anti-SARS-CoV-2 infection activity in a cell-based assay with an EC50 value of 0.42 M and 0.33 M, respectively. The X-ray crystal structures of SARS-CoV-2 Mpro in complex with 11a and 11b were determined at 1.5 [A] resolution, respectively. The crystal structures showed that 11a and 11b are covalent inhibitors, the aldehyde groups of which are bound covalently to Cys145 of Mpro. Both compounds showed good PK properties in vivo, and 11a also exhibited low toxicity which is promising drug leads with clinical potential that merits further studies.

biochemistry↗

bioRxiv2020

Morphological profiling of tubercule bacilli identifies drug pathways of action

Morphological profiling is a method to classify target pathways of antibacterials based on how bacteria respond to treatment through changes to cellular shape and spatial organization. Here, we utilized the cell-to-cell variation in morphological features of Mycobacterium tuberculosis bacilli to develop a rapid profiling platform called Morphological Evaluation and Understanding of Stress (MorphEUS). MorphEUS classified 94% of tested drugs correctly into broad categories according to modes of action previously identified in the literature. In the other 6%, MorphEUS pointed to key off-target or secondary bactericidal activities. We observed cell-wall damaging activity induced by bedaquiline and moxifloxacin through secondary effects downstream from their main target pathways. We implemented MorphEUS to correctly classify three compounds in a blinded study and identified an off-target effect for one compound that was not readily apparent in previous studies. We anticipate that the ability of MorphEUS to rapidly identify pathways of drug action and the proximal cause of bactericidal activity in tubercule bacilli will make it applicable to other pathogens and cell types where morphological responses are subtle and heterogeneous. Significance StatementTuberculosis is a leading cause of death in the world and requires treatment with an arduous multidrug regimen. Many new tuberculosis drugs are in development, and the drug development pipeline would benefit from more rapid methods to learn drug mechanism of action and off-target effects. Here, we describe a high throughput imaging method for rapidly classifying drugs into categories based on the primary and secondary cellular damage called Morphological Evaluation and Understanding of drug-Stress (MorphEUS). We anticipate that MorphEUS will assist in rapidly pinpointing causes of cellular death in response to drug treatment in tuberculosis and other bacterial pathogens.

microbiology↗

bioRxiv2020

Tracing the origin of a new organ by inferring the genetic basis of rumen evolution

The rumen is the hallmark organ of ruminants and hosts a diverse ecosystem of microorganisms that facilitates efficient digestion of plant fibers. We used 897 transcriptomes from three Cetartiodactyla lineages: ruminants, camels and cetaceans, as well as data from ruminant comparative genomics and functional assays to explore the genetic basis of rumen origin and evolution. Comparative analyses reveal that the rumen and the first-chamber stomachs of camels and cetaceans shared a common tissue origin from the esophagus. The rumen recruited genes from other tissues/organs and up-regulated many esophagus genes to aquire functional innovations involving epithelium absorption, improvement of the ketone body metabolism and regulation of microbial community. These innovations involve such genetic changes as ruminant-specific conserved elements, newly evolved genes and positively selected genes. Our in vitro experiements validate the functions of one enhancer, one positively selected gene and two newly evolved antibacterial genes. Our study provides novel insights into the origin and evolution of a complex organ.

evolutionary biology↗

bioRxiv2020

Common postzygotic mutational signature in multiple healthy adult tissues related to embryonic hypoxia

Postzygotic mutations are acquired in all of the normal tissues throughout an individuals lifetime and hold clues for identifying mutagenesis causing factors. The process and underlying mechanism of postzygotic mutations in normal tissues is still poorly understood. In this study, we investigated postzygotic mutation spectra in healthy individuals by optimized ultra-deep exome sequencing of time series samples from the same volunteer and samples from different individuals. In cells of blood, sperm, and muscle, we resolved three common types of mutational signature. Two of them are known to represent clock-like mutational processes, and their proportions in mutation profiles associated with polymorphisms of epigenetic regulation genes, suggesting the contribution of personal genetic backgrounds to underlying biological process. Notably, the third signature, characterized by C>T transitions at GpCpN sites, tends to be a feature of diverse normal tissues. Mutations of this type were likely to occur early in embryo development even before the tissue differentiation, as indicated by their relatively high allele frequencies, sharing variants between multiple tissues, and lacking of age-related accumulation. Almost all tumors shown in public datasets did not have this signature detected except for 19.6% of clear cell renal cell carcinoma samples, which featured by activation of the hypoxia-induced signaling pathway. Moreover, in vitro activation of HIF signaling pathway successfully introduced the corresponding mutation profile of this signature in a culture-expanded human embryonic stem cell line. Therefore, embryonic hypoxia may explain this novel signature across multiple normal tissues. Our study suggest hypoxic conditions in the early stage of embryo development may be a crucial factor for the C>T transitions at GpCpN sites and individual genetic background also related to shaping human postzygotic mutation profiles.

genetics↗

bioRxiv2020

Synergism and antagonism of two distinct, but confused, Nrf1 factors in integral regulation of the nuclear-to mitochondrial respiratory and antioxidant transcription networks

There is hitherto no literature available for explaining two distinct, but confused Nrf1 transcription factors, because they shared the same abbreviations from nuclear factor erythroid 2-related factor 1 (also called Nfe2l1) and nuclear respiratory factor (originally designated -Pal). Thus, we have here identified that Nfe2l1Nrf1 and -PalNRF1 exert synergistic and antagonistic roles in integrative regulation of the nuclear-to-mitochondrial respiratory and antioxidant transcription profiles. In mouse embryonic fibroblasts (MEFs), knockout of Nfe2l1-/- leads to substantial decreases in expression levels of -PalNRF1 and Nfe2l2, together with TFAM (mitochondrial transcription factor A) and other target genes. Similar inhibitory results were determined in Nfe2l2-/- MEFs, with an exception that GSTa1 and Aldh1a1 were distinguishably up-regulated in Nfe2l1-/- MEFs. Such synergistic contributions of Nfe2l1 and Nfe2l2 to the positive regulation of -PalNRF1 and TFAM were validated in Keap1-/- MEFs. However, human -PalNRF1 expression was unaltered by hNfe2l1-/-, hNfe2l2-/-{Delta}TA or even hNfe2l1-/-+siNrf2, albeit TFAM was activated by Nfe2l1 but inhibited by Nfe2l2; such an antagonism occured in HepG2 cells. Conversely, almost all of mouse Nfe2l1, Nfe2l2 and co-target genes were down-expressed in -PalNRF1+/- MEFs. On the contrary, up-regulation of human Nfe2l1, Nfe2l2 and relevant reporter genes took place after silencing of -PalNRF1, but their down-regulation occurred upon ectopic expression of -PalNRF1. Furtherly, Pitx2 (pituitary homeobox 2) was also identified as a direct upstream regulator of Nfe2l1 and TFAM, besides -PalNRF1. Overall, these across-talks amongst Nfe2l1, Nfe2l2 and -PalNRF1, along with Pitx2, are integrated from the endoplasmic reticulum to the nuclear-to-mitochondrial communication for targeting TFAM, in order to finely tune the cellular respiratory and antioxidant gene transcription networks, albeit they differ between the mouse and the human.

molecular biology↗

bioRxiv2020

Potent neutralization of 2019 novel coronavirus by recombinant ACE2-Ig

2019-nCoV, which is a novel coronavirus emerged in Wuhan, China, at the end of 2019, has caused at least infected 11,844 as of Feb 1, 2020. However, there is no specific antiviral treatment or vaccine currently. Very recently report had suggested that novel CoV would use the same cell entry receptor, ACE2, as the SARS-CoV. In this report, we generated a novel recombinant protein by connecting the extracellular domain of human ACE2 to the Fc region of the human immunoglobulin IgG1. An ACE2 mutant with low catalytic activity was also used in the study. The fusion proteins were then characterized. Both fusion proteins has high affinity binding to the receptor-binding domain (RBD) of SARS-CoV and 2019-nCoV and exerted desired pharmacological properties. Moreover, fusion proteins potently neutralized SARS-CoV and 2019-nCoV in vitro. As these fusion proteins exhibit cross-reactivity against coronaviruses, they could have potential applications for diagnosis, prophylaxis, and treatment of 2019-nCoV.

bioengineering↗

bioRxiv2019

Multinational qEEG developmental surfaces

The quantitative electroencephalogram (qEEG) is a diagnostic method based on the spectral features of the resting state EEG. The departure of spectral features from normality is gauged by the z transform with respect to the age-adjusted mean and deviation of normative databases - known as the developmental equations/surfaces. However, the extent to which the data collected from different countries with various equipment require separate developmental equations remains unanswered. Here, we analyzed the EEG of 535 subjects from 3 countries, Switzerland, the USA and Cuba. The EEG power spectra of all samples were log transformed and their relations to the covariables ( age, frequency, country and individual) were analyzed using the linear mixed effects model. We found that the origin country of the subjects did not play a significant effect on the log spectra, even without interactions with other independent variables, whereas, age and frequency were highly significant. To estimate the developmental surfaces in greater detail, we carried out kernel regression (lowess) in two dimensions of log-age and frequency. We found two main phenomena: 1) slow rhythms ({delta}, {theta}) predominated in the lower ages and then decreased with a tendency to disappear at higher ages; 2) rhythm was absent at lower ages, but gradually appeared more relevant in occipital and parietal regions, and increased with aging with an increasing centering frequency of rhythm. We consider both phenomena as an expression of healthy neurodevelopmental and maturation related to age. It is the first study of multinational qEEG developmental surfaces accounting for country. The results demonstrate the possibility of creating international qEEG norms since the individual and age variability are much larger than the specific factors like country, or the technology employed device.

neuroscience↗

bioRxiv2019

Xi rhythms: decoding neural oscillations to create full brain high resolution spectra parametric mapping

Neural oscillations excitability shape sensory, motor, and cognitive processes of the brain operation. To quantify the spectrum of brain magnetic and electrical recordings has become the main methodology to study neural oscillations. However, there is still lacking a valid approach, although the literatures on the spectrum decomposition is vast. In this work, we fit the neural spectrum by means of the Expectation Maximization algorithm, where the E step turns into a Winner filtering to separate multiple components and the M step is to fit each component by minimizing the smoothness penalized Whittle likelihood and shape-restricted regression, say, monotonicity, that is able to fit the diverse shape of each component. The decomposition allows characterizing the oscillation amplitude, resonance frequency, bandwidth, skewness, kurtosis, and slope of each component. This approach is termed as Xi rhythms, with Xi and rhythms standing for the background activity and multiple peaks. We apply it to: 1) multinational EEG database consisting of 535 subjects to create the quantitative spectrum norms (QSN); 2) large sample intracranial EEG (iEEG) dataset to infer the oscillations from recorded region to unrecorded areas within one subject and over inter-individuals and create the full brain high resolution statistical spectra parametric mapping. The statistical spectrum parameter mapping of iEEG promisingly provides an atlas and creates a norm for neural oscillations and quantitative electrophysiology study which can gain us more insightful understanding to brain dynamics, cognitive process and mental disorders.

neuroscience↗

bioRxiv2019

Antibody Bank: the Synthetic Cell Repertoire for Immunotherapy

The immune surveillance hypothesis is regarded as the intellectual underpinning of cancer immunology. We find that engineered T cell library displaying CAR constructs, where the antibody repertoires took the place of the antigen-recognition region, has the capacity to recognize nonself-antigens and showed antigen dependent clonal expanding and persistence. This process coupled with long-lasting anti-tumour effect in a broad spectrum of epithelial tumours. Moreover, CAR-T library showed robust immunologic memory and maintenance of diversity to recognize mutated or evolved tumours in both immunodeficiency and immunoresponsive murine tumor models. Large CAR library was further developed in logic-gated NK-92 cells to develop an off-the shelf therapeutic library. Thus, the biological behaviour of synthetic cell library is highly accordance with the immune surveillance function, which proved the way to rebuilt functional MHC unrestricted cellular immunity in vitro using synthetic method.

bioengineering↗

bioRxiv2019

TIGIT-Fc Promote Immune Tolerance at the Feto-maternal Interface

The perfect synchronization of maternal immune-endocrine mechanisms and those of the foetus is necessary for a successful pregnancy. In this report, decidual immune cells at the maternal-foetal interface were detected that expressed TIGIT (T cell immunoreceptor with Ig and ITIM domains), which is a co-inhibitory receptor that triggers immunological tolerance. We generated recombinant TIGIT-Fc fusion proteins by linking the extracellular domain of TIGIT and silent Fc fragments. The treatment with TIGIT-Fc of human decidual dendritic cells (dDCs) increased the production of interleukin 10 and induced the dDCs to powerfully polarize the decidual CD4+ T cells towards a classic TH2 phenotype. The administration of TIGIT-Fc to CBA/J pregnant mice at preimplantation induced CD4+ forkhead box P3+ (Foxp3+) regulatory T cells and tolerogenic dendritic cells and increased pregnancy rates in a mouse model of abortive stress. Moreover, we proposed that progesterone play a direct role in the transcriptional regulation of the TIGIT gene in decidual immune cell subsets. The results suggested the therapeutic potential of the TIGIT-Fc fusion protein in reinstating immune tolerance in failing pregnancies.

immunology↗

bioRxiv2019

Screening and identification of MicroRNAs expressed in perirenal adipose tissue during rabbit growth

MiRNAs regulate adipose tissue development, which are closely related to subcutaneous and intramuscular fat deposition and adipocyte differentiation. As an important economic and agricultural animal, rabbits have low adipose tissue deposition and are an ideal model to study adipose regulation. However, the miRNAs related to fat deposition during the growth and development of rabbits are poorly defined. In this study, miRNA-sequencing and bioinformatics analyses were used to profile the miRNAs in rabbit perirenal adipose tissue at 35, 85 and 120 days post-birth. Differentially expressed (DE) miRNAs between different stages were identified by DEseq in R. Target genes of DE miRNAs were predicted by TargetScan and miRanda. To explore the functions of identified miRNAs, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Approximately 1.6 GB of data was obtained by miRNA-seq. A total of 987 miRNAs (780 known and 207 newly predicted) and 174 DE miRNAs were identified. The miRNAs ranged from 18nt to 26nt. GO enrichment and KEGG pathway analyses revealed that the target genes of the DE miRNAs were mainly involved in zinc ion binding, regulation of cell growth, MAPK signaling pathway, and other adipose hypertrophy-related pathways. Six DE miRNAs were randomly selected and their expression profiles were validated by q-PCR. In summary, we provide the first report of the miRNA profiles of rabbit adipose tissue during different growth stages. Our data provide a theoretical reference for subsequent studies on rabbit genetics, breeding and the regulatory mechanisms of adipose development.

developmental biology↗

bioRxiv2019

Epicardial therapy with atrial appendage micrografts salvages myocardium after infarction

Ischemic heart disease remains the leading cause of mortality and morbidity worldwide despite improved possibilities in medical care. Alongside interventional therapies, such as coronary artery bypass grafting, adjuvant tissue-engineered and cell-based treatments can provide regenerative improvement. Unfortunately, most of these advanced approaches require multiple lengthy and costly preparation stages without delivering significant clinical benefits.\n\nWe evaluated the effect of epicardially delivered minute pieces of atrial appendage tissue material, defined as atrial appendage micrografts (AAMs), in mouse myocardial infarction model. An extracellular matrix patch was used to cover and fix the AAMs onto the surface of the infarcted heart. The matrix-covered AAMs salvaged the heart from infarction-induced loss of functional myocardium and attenuated scarring. Site-selective proteomics of injured ischemic and uninjured distal myocardium from AAM-treated and untreated tissue sections revealed an increased expression of several cardiac regeneration-associated proteins (i.e. periostin, transglutaminases and glutathione peroxidases) as well as activation of pathways responsible for angio- and cardiogenesis in relation to AAMs therapy.\n\nEpicardial delivery of AAMs encased in an extracellular matrix patch scaffold salvages functional cardiac tissue from ischemic injury and restricts fibrosis after myocardial infarction. Our results support the use of AAMs as tissue-based therapy adjuvants for salvaging the ischemic myocardium.

bioinformatics↗

bioRxiv2019

Networks of enhancers and microRNAs drive variation in cell states

Cell-to-cell variation in gene expression is a common feature of developmental processes. Yet, it remains unclear whether molecular mediators can generate variation and how this process is coordinated across loci to allow the emergence of new cell states. Using embryonic stem cells (ESCs) as a model of development, we found interconverting cell states that resemble developmental expression programs and vary in activity at specific enhancers, such as those regulating pluripotency genes Nanog and Sox2 but not Pou5f1 (Oct4). Variable enhancers drive expression of variable genes, including those encoding microRNAs (miRNAs). Notably, variable miRNAs increase cell-to-cell variation by acting on neighborhoods of pluripotency genes. The encoded, variable pluripotency factors bind variable enhancers, forming a feedback loop that amplifies variation and allows the emergence of new cell states. These findings suggest gene regulatory networks composed of enhancers, protein-coding genes, and miRNAs harness inherent variation into developmental outcomes.

cell biology↗

bioRxiv2019

The identification of mecciRNAs and their roles in mitochondrial entry of proteins

Mammalian mitochondria have small genomes encoding very limited numbers of proteins. Over one thousand proteins and noncoding RNAs encoded by nuclear genome have to be imported from the cytosol into the mitochondria. Here we report the identification of hundreds of circular RNAs (mecciRNAs) encoded by mitochondrial genome. We provide both in vitro and in vivo evidence to show that mecciRNAs facilitate mitochondrial entry of nuclear-encoded proteins by serving as molecular chaperones in the folding of imported proteins. Known components of mitochondrial protein and RNA importation such as TOM40 and PNPASE interact with mecciRNAs and regulate protein entry. Expression of mecciRNAs is regulated, and these transcripts are critical for mitochondria in adapting to physiological conditions and diseases such as stresses and cancers by modulating mitochondrial protein importation. mecciRNAs and their associated physiological roles add categories and functions to eukaryotic circular RNAs, and shed novel lights on communication between mitochondria and nucleus.

molecular biology↗

bioRxiv2019

A unity of opposites in between Nrf1- and Nrf2-mediated responses to the endoplasmic reticulum stressor tunicamycin

The water-soluble Nrf2 is accepted as a master regulator of antioxidant responses to cellular stress, it was also identified as a direct target of the endoplasmic reticulum (ER)-anchored PERK. However, the membrane-bound Nrf1 response to ER stress remains elusive. Herein, we report a unity of opposites in both Nrf1- and Nrf2-coordinated responses to the ER stressor tunicamycin (TU). The TU-inducible transcription of Nrf1 and Nrf2, as well as GCLM and HO-1, was accompanied by activation of ER stress signaling networks. The unfolded protein response (UPR) mediated by ATF6, IRE1 and PERK was significantly suppressed by Nrf1-specific knockout, but hyper-expression of Nrf2, GCLM and HO-1 was retained in Nrf1-/- cells. By contrast, Nrf2-/-{Delta}TA cells with a genomic deletion of its transactivation domain resulted in significant decreases of GCLM, HO-1 and Nrf1; this was accompanied by partial decreases of IRE1 and ATF6, but not PERK, along with an obvious increase of ATF4. Notably, Nrf1 glycosylation and its trans-activity to mediate transcriptional expression of 26S proteasomal subunits were repressed by TU. This inhibitory effect was enhanced by Nrf1-/- and Nrf2-/-{Delta}TA, but not by a constitutive activator caNrf2{Delta}N (that increased abundances of non-glycosylated and processed Nrf1). Furthermore, caNrf2{Delta}N also enhanced induction of PERK and IRE1 by TU, but reduced expression of ATF4 and HO-1. Such distinct roles of Nrf1 and Nrf2 are unified to maintain cell homeostasis by a series of coordinated ER-to-nuclear signaling responses to TU. Overall, Nrf1 acts in a cell-autonomous manner to determine transcription of most of UPR-target genes, albeit Nrf2 is also partially involved in this process.

molecular biology↗

bioRxiv2019

Slc7a11 modulated by POU2F1 is involved in pigmentation in rabbit

Solute carrier family 7 member 11 (Slc7a11) codes for a cystine/glutamate xCT transporter and can control production of pheomelanin pigment to change fur and skin colors of animals. Previous studies found that the skin expression levels of Slc7a11 varied significantly with the fur colors of the Rex Rabbit. However, it is not yet known the molecular regulation mechanism of Slc7a11 in pigmentation. Here rabbit melanocytes were first isolated and identified. The distribution and expression pattern of Slc7a11 was confirmed in rabbit skin with different fur colors. Slc7a11 could affect the expression of pigmentation related genes and thus affect melanogenesis. Meanwhile, Slc7a11 decreased melanocytes apoptosis, but inhibition of Slc7a11 enhanced apoptosis. Furthermore, it was found that POU2F1 protein bound to the -713 to -703 bp region of Slc7a11 promoter to inhibite its activity by dual-luciferase reporter and site-directed mutagenesis assay. This study uncover the function of the Slc7a11 in melanogenesis and provided in-depth analysis of the mechanism of fur pigmentation.

molecular biology↗