Adsorption performance of polydopamine-modified attapulgite granular adsorbent for methylene blue.

Polydopamine-modified granule organo-attapulgite adsorbent (PDA-GOAT) was facilely prepared via a dip-coating approach. The samples were characterized by scanning electron microscopy, X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. Surface area and pore size were calculated from the Brunauer-Emmett-Teller method by N2 adsorption-desorption isotherm. The adsorption behaviour of methylene blue (MB) onto PDA-GOAT was systematically investigated. The experimental data revealed that the adsorption process fitted well with the pseudo-second-order kinetics equation and the adsorption isotherm fitted better with the Langmuir model. Thermodynamic analyses illustrated that MB adsorption onto PDA-GOAT was a physisorption endothermic process. Importantly, PDA-GOAT can be regenerated by NaBH4 aqueous solution. The obtained results prove that PDA-GOAT can be a superior reusable adsorbent for the removal of MB from effluent.

Nucleosome organizations in induced pluripotent stem cells reprogrammed from somatic cells belonging to three different germ layers.

BACKGROUND: Nucleosome organization determines the chromatin state, which in turn controls gene expression or silencing. Nucleosome remodeling occurs during somatic cell reprogramming, but it is still unclear to what degree the re-established nucleosome organization of induced pluripotent stem cells (iPSCs) resembles embryonic stem cells (ESCs), and whether the iPSCs inherit some residual gene expression from the parental fibroblast cells. RESULTS: We generated genome-wide nucleosome maps in mouse ESCs and in iPSCs reprogrammed from somatic cells belonging to three different germ layers using a secondary reprogramming system. Pairwise comparisons showed that the nucleosome organizations in the iPSCs, regardless of the iPSCs' tissue of origin, were nearly identical to the ESCs, but distinct from mouse embryonic fibroblasts (MEF). There is a canonical nucleosome arrangement of -1, nucleosome depletion region, +1, +2, +3, and so on nucleosomes around the transcription start sites of active genes whereas only a nucleosome occupies silent transcriptional units. Transcription factor binding sites possessed characteristic nucleosomal architecture, such that their access was governed by the rotational and translational settings of the nucleosome. Interestingly, the tissue-specific genes were highly expressed only in the parental somatic cells of the corresponding iPS cell line before reprogramming, but had a similar expression level in all the resultant iPSCs and ESCs. CONCLUSIONS: The re-established nucleosome landscape during nuclear reprogramming provides a conserved setting for accessibility of DNA sequences in mouse pluripotent stem cells. No persistent residual expression program or nucleosome positioning of the parental somatic cells that reflected their tissue of origin was passed on to the resulting mouse iPSCs.

Phylogenetic affinity of tree shrews to Glires is attributed to fast evolution rate.

Previous phylogenetic analyses have led to incongruent evolutionary relationships between tree shrews and other suborders of Euarchontoglires. What caused the incongruence remains elusive. In this study, we identified 6845 orthologous genes between seventeen placental mammals. Tree shrews and Primates were monophyletic in the phylogenetic trees derived from the first or/and second codon positions whereas tree shrews and Glires formed a monophyly in the trees derived from the third or all codon positions. The same topology was obtained in the phylogeny inference using the slowly and fast evolving genes, respectively. This incongruence was likely attributed to the fast substitution rate in tree shrews and Glires. Notably, sequence GC content only was not informative to resolve the controversial phylogenetic relationships between tree shrews, Glires, and Primates. Finally, estimation in the confidence of the tree selection strongly supported the phylogenetic affiliation of tree shrews to Primates as a monophyly.

Novel strategy for copper precipitation from cupric complexes wastewater: Catalytic oxidation or reduction self-decomplexation?

Cupric (Cu(II)) complexes in industrial wastewater are responsible for the failure of conventional alkaline precipitation, but the properties of cuprous (Cu(I)) complexes at alkaline circumstance have not been focused. This report proposed a novel strategy for the remediation of Cu(II)-complexed wastewater by coupling alkaline precipitation with green benign reductant, namely, hydroxylamine hydrochloride (HA). This remediation process (HA-OH) exhibits superior Cu removal efficiency that cannot be achieved with the same dosage of oxidants (3 mM). The possibility of Cu(I) activated O2 catalysis and self-decomplexation precipitation were investigated, and the results identified that 1O2 was generated from Cu(II)/Cu(I) cycle, but it was insufficient to annihilate organic ligands. Cu(I) self-decomplexation was the dominate mechanism of Cu removal. For real industrial wastewater, HA-OH process can realize the efficient Cu2O precipitation and Cu recovery. This novel strategy utilized intrinsic pollutant in wastewater without introducing other metals, complicated materials, and expensive equipment, broadening the insight for the remediation of Cu(II)-complexed wastewater.

Transcriptome profiles and chromatin states in mouse androgenetic haploid embryonic stem cells.

Haploid embryonic stem cells (haESCs) are derived from the inner cell mass of the haploid blastocyst, containing only one set of chromosomes. Extensive and accurate chromatin remodelling occurs during haESC derivation, but the intrinsic transcriptome profiles and chromatin structure of haESCs have not been fully explored. We profiled the transcriptomes, nucleosome positioning, and key histone modifications of four mouse haESC lines, and compared these profiles with those of other closely-related stem cell lines, MII oocytes, round spermatids, sperm, and mouse embryonic fibroblasts. haESCs had transcriptome profiles closer to those of naïve pluripotent stem cells. Consistent with the one X chromosome in haESCs, Xist was repressed, indicating no X chromosome inactivation. haESCs and ESCs shared a similar global chromatin structure. However, a nucleosome depletion region was identified in 2056 promoters in ESCs, which was absent in haESCs. Furthermore, three characteristic spatial relationships were formed between transcription factor motifs and nucleosomes in both haESCs and ESCs, specifically in the linker region, on the nucleosome central surface, and nucleosome borders. Furthermore, the chromatin state of 4259 enhancers was off in haESCs but active in ESCs. Functional annotation of these enhancers revealed enrichment in regulation of the cell cycle, a predominantly reported mechanism of haESC self-diploidization. Notably, the transcriptome profiles and chromatin structure of haESCs were highly preserved during passaging but different from those of differentiated cell types.

Deep learning model accurately classifies metastatic tumors from primary tumors based on mutational signatures.

Metastatic propagation is the leading cause of death for most cancers. Prediction and elucidation of metastatic process is crucial for the treatment of cancer. Even though somatic mutations have been linked to tumorigenesis and metastasis, it is less explored whether metastatic events can be identified through genomic mutational signatures, which are concise descriptions of the mutational processes. Here, we developed MetaWise, a Deep Neural Network (DNN) model, by applying mutational signatures as input features calculated from Whole-Exome Sequencing (WES) data of TCGA and other metastatic cohorts. This model can accurately classify metastatic tumors from primary tumors and outperform traditional machine learning (ML) models and a deep learning (DL) model, DiaDeL. Signatures of non-coding mutations also have a major impact on the model's performance. SHapley Additive exPlanations (SHAP) and Local Surrogate (LIME) analyses identify several mutational signatures which are directly correlated to metastatic spread in cancers, including APOBEC-mutagenesis, UV-induced signatures, and DNA damage response deficiency signatures.

Using graph-based model to identify cell specific synthetic lethal effects.

Synthetic lethal (SL) pairs are pairs of genes whose simultaneous loss-of-function results in cell death, while a damaging mutation of either gene alone does not affect the cell's survival. This makes SL pairs attractive targets for precision cancer therapies, as targeting the unimpaired gene of the SL pair can selectively kill cancer cells that already harbor the impaired gene. Limited by the difficulty of finding true SL pairs, especially on specific cell types, current computational approaches provide only limited insights because of overlooking the crucial aspects of cellular context dependency and mechanistic understanding of SL pairs. As a result, the identification of SL targets still relies on expensive, time-consuming experimental approaches. In this work, we applied cell-line specific multi-omics data to a specially designed deep learning model to predict cell-line specific SL pairs. Through incorporating multiple types of cell-specific omics data with a self-attention module, we represent gene relationships as graphs. Our approach achieves the prediction of SL pairs in a cell-specific manner and demonstrates the potential to facilitate the discovery of cell-specific SL targets for cancer therapeutics, providing a tool to unearth mechanisms underlying the origin of SL in cancer biology. The code and data of our approach can be found at https://github.com/promethiume/SLwise.

Assembly of UiO-66 onto Co-doped Fe3O4 nanoparticles to activate peroxymonosulfate for efficient degradation of fenitrothion and simultaneous in-situ adsorption of released phosphate.

Although sulfate radical-based advanced oxidation processes (SR-AOPs) have shown great potential for the efficient degradation of various organic contaminants, there is few research on the removal of organophosphorus pesticides (OPPs) through SR-AOPs. In this work, Co-doped Fe3O4 magnetic particles encapsulated by zirconium-based metal-organic frameworks (Co-Fe3O4@UiO-66) were prepared and employed to activate peroxymonosulfate (PMS) for the elimination of fenitrothion (FNT) and the simultaneous in-situ adsorption of produced phosphate. The catalyst exhibited efficient catalytic performance, achieving above 90.0% removal of FNT (10 mg/L) in the presence of PMS (1 mM) within 60 min. Moreover, the produced phosphate during the degradation process was also completely adsorbed onto the catalyst. Both sulfate and hydroxyl radicals were responsible for the degradation of FNT. The degradation products of FNT in the system were identified and the possible pathways were proposed. This study represents a promising and adoptable strategy to develop other versatile composite nanomaterials in a green manner hence broadening its environmental application range, as it can not only remove OPPs by catalytic oxidation but also immobilize degraded phosphorus by adsorption.

Surface molecular imprinting on polystyrene resin for selective adsorption of 4-hydroxybenzoic acid.

Using chloromethylated polystyrene resin, N,N-diethylaminoethyl methacrylate, and ethylene glycol dimethacrylate as support, functional monomer and cross-linker, respectively, the molecularly imprinted resin (MIR) and non-imprinted resin (NIR) were fabricated by the combination of atom transfer radical polymerization and surface imprinting technique for the selective adsorption of 4-hydroxybenzoic acid (4-HB) from aqueous solutions. The prepared adsorbents were characterized by N2 adsorption/desorption isotherms, Fourier-transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The adsorption processes of the 4-HB with MIR and NIR followed pseudo-second-order kinetics, and the adsorption isotherms were appreciably described by the Langmuir model. Furthermore, the adsorption efficiencies of MIR and NIR for different compounds in single and binary solutions proved that MIR exhibited high adsorption capacity and favorable selectivity toward 4-HB over other structurally related organic compounds (i.e., benzoic acid, 2-hydroxybenzoic acid, 3-hydroxybenzoic acid, phenol, and 2-hydroxynaphthalene). In addition, MIR could effectively remove 4-HB from a simulated effluent in a dynamic adsorption experiment. This study illustrates in-depth perspectives on the adsorption mechanisms of 4-HB onto MIR; interactions between the adsorbate and adsorbent were proposed based on the adsorption behaviours and instrumental analyses. The resulting MIR is a promising material for the interference-free adsorbent in the selective adsorption of 4-HB from mixed solutions.

Facile synthesis of core-shell phase-transited lysozyme coated magnetic nanoparticle as a novel adsorbent for Hg(II) removal in aqueous solutions.

Adsorption using nanomaterials is considered an effective method for controlling the levels of toxic heavy metal in wastewater. Herein, a novel adsorbent, core-shell phase-transited lysozyme film-coated magnetic nanoparticles (Fe3O4@SiO2@PTL) for Hg(II) ions removal from aqueous solutions was explored via facile and fast phase transformation and self-assembly process of lysozyme. The physiochemical properties of Fe3O4@SiO2@PTL were investigated using various characterization techniques. The adsorption performances such as kinetics, isotherms, selectivity, the effect of coexisting ions, and regeneration were evaluated. Fe3O4@SiO2@PTL showed an extremely high Hg(II) uptake rate and achieved more than 90% equilibrium adsorption capacity in 5 min. Hg(II) adsorption was followed by a pseudo-second-order kinetic model and fitted the Langmuir model by achieving a maximum uptake of 701.51 mg/g. Furthermore, excellent Hg(II) selectivity was obtained in a mixed solution containing various heavy metal ions, along with good chemical stability owing to the high adsorption capacity maintained after five cycles. The adsorption analyses indicated that the amino, imino, amide, hydroxyl, carboxyl, and thiol groups exposed on the surface of Fe3O4@SiO2@PTL were vital for Hg(II) removal. Consequently, this work will significantly assist in the development of an easily available, eco-friendly, and selective adsorbent material to remove heavy metal ions from wastewater.

Differential Transcriptomes and Methylomes of Trophoblast Stem Cells From Naturally-Fertilized and Somatic Cell Nuclear-Transferred Embryos.

Trophoblast stem cells (TSCs) are critical to mammalian embryogenesis by providing the cell source of the placenta. TSCs can be derived from trophoblast cells. However, the efficiency of TSC derivation from somatic cell nuclear transfer (NT) blastocysts is low. The regulatory mechanisms underlying transcription dynamics and epigenetic landscape remodeling during TSC derivation remain elusive. Here, we derived TSCs from the blastocysts by natural fertilization (NF), NT, and a histone deacetylase inhibitor Scriptaid-treated NT (SNT). Profiling of the transcriptomes across the stages of TSC derivation revealed that fibroblast growth factor 4 (FGF4) treatment resulted in many differentially expressed genes (DEGs) at outgrowth and initiated transcription program for TSC formation. We identified 75 transcription factors (TFs) that are continuously upregulated during NF TSC derivation, whose transcription profiles can infer the time course of NF not NT TSC derivation. Most DEGs in NT outgrowth are rescued in SNT outgrowth. The correct time course of SNT TSC derivation is inferred accordingly. Moreover, these TFs comprise an interaction network important to TSC stemness. Profiling of DNA methylation dynamics showed an extremely low level before FGF4 treatment and gradual increases afterward. FGF4 treatment results in a distinct DNA methylation remodeling process committed to TSC formation. We further identified 1,293 CpG islands (CGIs) whose DNA methylation difference is more than 0.25 during NF TSC derivation. The majority of these CGIs become highly methylated upon FGF4 treatment and remain in high levels. This may create a barrier for lineage commitment to restrict embryonic development, and ensure TSC formation. There exist hundreds of aberrantly methylated CGIs during NT TSC derivation, most of which are corrected during SNT TSC derivation. More than half of the aberrantly methylated CGIs before NT TSC formation are inherited from the donor genome. In contrast, the aberrantly methylated CGIs upon TSC formation are mainly from the highly methylated CGIs induced by FGF4 treatment. Functional annotation indicates that the aberrantly highly methylated CGIs play a role in repressing placenta development genes, etc., related to post-implantation development and maintaining TSC pluripotency. Collectively, our findings provide novel insights into the transcription dynamics, DNA methylation remodeling, and the role of FGF4 during TSC derivation.

Polyethylenimine-functionalized polyacrylonitrile anion exchange fiber as a novel adsorbent for rapid removal of nitrate from wastewater.

The development of an adsorbent with high adsorption ability and favorable cyclic regeneration performance for the removal of nitrate residues from wastewater is a task of vital importance. To this end, polyacrylonitrile fiber (PANF) was modified with polyethyleneimine (PEI), and alkyl groups were then introduced around the active amine groups to prepare three polymer-based anion exchange fibers (PAN-PEI-3C, PAN-PEI-5C, and PAN-PEI-8C). The novel fibers were characterized using techniques such as scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA). The adsorption isotherms of the fibers were best fitted by the Langmuir model, and PAN-PEI-5C exhibited a higher adsorption amount of nitrate (31.32 mg/g) than the other adsorbents. The equilibrium was reached expeditiously (within 10 min), and both pseudo-first-order and pseudo-second-order models could well describe the adsorption kinetics. More attractively, the saturated PAN-PEI-5C could be eluted using a low-concentration (0.3 M) NaCl solution, without any sharp loss of adsorption amount for five consecutive cycles in the presence of dissolved organic matter (DOM). Furthermore, PAN-PEI-5C could effectively adsorb low-concentration nitrate from real secondary effluents in a fixed-bed column experiment. Our work provides a promising and low-cost material for the removal of nitrate residues in practical applications.

Curcumin micelles suppress gastric tumor cell growth by upregulating ROS generation, disrupting redox equilibrium and affecting mitochondrial bioenergetics.

Gastric cancer is the fourth most common cancer and the second most frequent cause of cancer death worldwide. Chemotherapy is an important treatment. However, traditional chemotherapy drugs have low bioavailability and targeting ability. Therefore, we developed curcumin-encapsulated micelles for the treatment of gastric cancer and investigated their antitumor efficacy and active mechanism. Gastric cancer cells were treated with different concentrations of curcumin micelles. MTS cell proliferation assays, flow cytometry (FCM), real time cellular analysis (RTCA) and nude mice xenografts were used to evaluate the effects of curcumin micelles on gastric cancer cell growth in vitro and in vivo. Western blotting was performed to analyze the protein levels of the indicated molecules. A Seahorse bioenergetics analyzer was used to investigate alterations in oxygen consumption and the aerobic glycolysis rate. Curcumin micelles significantly inhibited proliferation and colony formation and induced apoptosis in gastric tumor cells compared to the control groups. We further investigated the mechanism of curcumin micelles on gastric tumor cells and demonstrated that curcumin micelles acted on mitochondrial proteins, causing changes in mitochondrial function and affecting mitochondrial bioenergetics. Furthermore, curcumin micelles decreased mitochondrial membrane potential, increased reactive oxygen species (ROS) generation and disrupted redox equilibrium. The nude mouse model verified that curcumin micelle treatment significantly attenuated tumor growth in vivo. Curcumin micelles suppress gastric tumor cell growth in vitro and in vivo. The mechanism may be related to increasing ROS generation, disrupting redox equilibrium and affecting mitochondrial bioenergetics.

Increase in DNA Damage by MYCN Knockdown Through Regulating Nucleosome Organization and Chromatin State in Neuroblastoma.

As a transcription factor, MYCN regulates myriad target genes including the histone chaperone FACT. Moreover, FACT and MYCN expression form a forward feedback loop in neuroblastoma. It is unclear whether MYCN is involved in chromatin remodeling in neuroblastoma through regulation of its target genes. We showed here that MYCN knockdown resulted in loss of the nucleosome-free regions through nucleosome assembly in the promoters of genes functionally enriched for DNA repair. The active mark H3K9ac was removed or replaced by the repressive mark H3K27me3 in the promoters of double-strand break repair-related genes upon MYCN knockdown. Such chromatin state alterations occurred only in MYCN-bound promoters. Consistently, MYCN knockdown resulted in a marked increase in DNA damage in the treatment with hydroxyurea. In contrast, nucleosome reorganization and histone modification changes in the enhancers largely included target genes with tumorigenesis-related functions such as cell proliferation, cell migration, and cell-cell adhesion. The chromatin state significantly changed in both MYCN-bound and MYCN-unbound enhancers upon MYCN knockdown. Furthermore, MYCN knockdown independently regulated chromatin remodeling in the promoters and the enhancers. These findings reveal the novel epigenetic regulatory role of MYCN in chromatin remodeling and provide an alternative potential epigenetic strategy for MYCN-driven neuroblastoma treatment.

Ferroptosis is governed by differential regulation of transcription in liver cancer.

Ferroptosis is an outcome of metabolic disorders and closely linked to liver cancer. However, the mechanism underlying the fine regulation of ferroptosis in liver cancer remains unclear. Here, we have identified two categories of genes: ferroptosis up-regulated factors (FUF) and ferroptosis down-regulated factors (FDF), which stimulate and suppress ferroptosis by affecting the synthesis of GSH. Furthermore, FUF are controlled by one transcription factor HIC1, while FDF controlled by another transcription factor HNF4A. Occurrence of ferroptosis might depend on the histone acetyltransferase KAT2B. Upon stimulation of ferroptosis, dissociation of KAT2B prevents HNF4A from binding to the FDF promoter. This effect happens prior to the recruitment of KAT2B to the FUF promoter, which facilitates HIC1 binding to transcribe FUF. Clinically, HIC1 and HNF4A conversely correlate with tumor stage in liver cancer. Patients with lower HIC1 and higher HNF4A exhibit poorer prognostic outcomes. Disrupting the balance between HIC1 and HNF4A might be helpful in treating liver cancer.

circRNA_104075 stimulates YAP-dependent tumorigenesis through the regulation of HNF4a and may serve as a diagnostic marker in hepatocellular carcinoma.

Some types of circular RNA (circRNA) are aberrantly expressed in human diseases including hepatocellular carcinoma (HCC). However, its regulation mechanism and diagnostic roles are largely unknown. Here, we identified that circRNA_104075 (circ_104075) was highly expressed in HCC tissues, cell lines and serum. Mechanistically, HNF4a bound to the -1409 to -1401 region of the circ_104075 promoter to stimulate the expression of circ_104075. Moreover, circ_104075 acted as a ceRNA to upregulate YAP expression by absorbing miR-582-3p. Interestingly, an N6-methyladenosine (m6A) motif was identified in the 353-357 region of YAP 3'UTR, and this m6A modification was essential for the interaction between miR-582-3p and YAP 3'UTR. Further, the diagnostic performance of circ_104075 was evaluated. The area under the receiver operating characteristic (AUC-ROC) for circ_104075 was 0.973 with a sensitivity of 96.0% and a specificity of 98.3%. Collectively, we determined that circ_104075 was highly expressed in HCC and elucidated its upstream and downstream regulatory mechanisms. circ_104075 additionally has the potential to serve as a new diagnostic biomarker in HCC. Targeting circ_104075 may provide new strategies in HCC diagnosis and therapy.

Reduced Self-Diploidization and Improved Survival of Semi-cloned Mice Produced from Androgenetic Haploid Embryonic Stem Cells through Overexpression of Dnmt3b.

Androgenetic haploid embryonic stem cells (AG-haESCs) hold great promise for exploring gene functions and generating gene-edited semi-cloned (SC) mice. However, the high incidence of self-diploidization and low efficiency of SC mouse production are major obstacles preventing widespread use of these cells. Moreover, although SC mice generation could be greatly improved by knocking out the differentially methylated regions of two imprinted genes, 50% of the SC mice did not survive into adulthood. Here, we found that the genome-wide DNA methylation level in AG-haESCs is extremely low. Subsequently, downregulation of both de novo methyltransferase Dnmt3b and other methylation-related genes was determined to be responsible for DNA hypomethylation. We further demonstrated that ectopic expression of Dnmt3b in AG-haESCs could effectively improve DNA methylation level, and the high incidence of self-diploidization could be markedly rescued. More importantly, the developmental potential of SC embryos was improved, and most SC mice could survive into adulthood.

TFCP2 Is Required for YAP-Dependent Transcription to Stimulate Liver Malignancy.

Although YAP-dependent transcription is closely associated with liver tumorigenesis, the mechanism by which YAP maintains its function is poorly understood. Here, we show that TFCP2 is required for YAP-dependent transcription and liver malignancy. Mechanistically, YAP function is stimulated by TFCP2 via a WW-PSY interaction. TFCP2 also maintains YAP stability by inhibiting ßTrCP. Notably, genomic co-occupancy of YAP and TFCP2 is revealed. TFCP2 acts as a transcription co-factor that stimulates YAP transcription by facilitating YAP binding with YAP binding motif (YBF)-containing transcription factors. Interestingly, TFCP2 also stimulated the YAP-TEAD interaction and TEAD target gene expression. Finally, several genes co-regulated by YAP and TFCP2 that contribute to YAP-dependent tumorigenesis are identified and verified. Thus, we establish a model showing that TFCP2 acts as a YAP co-factor to maintain YAP-dependent transcription in liver cancer cells, suggesting that simultaneous targeting of both YAP and TFCP2 may be an effective therapeutic approach.

Global MicroRNA Expression Profiling of Mouse Livers following Ischemia-Reperfusion Injury at Different Stages.

Hepatic ischemia-reperfusion injury is a dynamic process consisting of two stages: ischemia and reperfusion, and triggers a cascade of physiological and biochemical events. Given the important role of microRNAs in regulating gene expression, we analyzed gene expression changes in mouse livers at sham control, ischemia stage, and reperfusion stage. We generated global expression profiles of microRNA and mRNA genes in mouse livers subjected to ischemia-reperfusion injury at the three stages, respectively. Comparison analysis showed that reperfusion injury had a distinct expression profile whereas the ischemia sample and the sham control were clustered together. Consistently, there are 69 differentially expressed microRNAs between the reperfusion sample and the sham control whereas 28 differentially expressed microRNAs between the ischemia sample and the sham control. We further identified two modes of microRNA expression changes in ischemia-reperfusion injury. Functional analysis of both the differentially expressed microRNAs in the two modes and their target mRNAs revealed that ischemia injury impaired mitochondrial function, nutrient consumption, and metabolism process. In contrast, reperfusion injury led to severe tissue inflammation that is predominantly an innate-immune response in the ischemia-reperfusion process. Our staged analysis of gene expression profiles provides new insights into regulatory mechanisms of microRNAs in mouse hepatic IR injury.

Hierarchical Oct4 Binding in Concert with Primed Epigenetic Rearrangements during Somatic Cell Reprogramming.

The core pluripotency factor Oct4 plays key roles in somatic cell reprogramming through transcriptional control. Here, we profile Oct4 occupancy, epigenetic changes, and gene expression in reprogramming. We find that Oct4 binds in a hierarchical manner to target sites with primed epigenetic modifications. Oct4 binding is temporally continuous and seldom switches between bound and unbound. Oct4 occupancy in most of promoters is maintained throughout the entire reprogramming process. In contrast, somatic cell-specific enhancers are silenced in the early and intermediate stages, whereas stem cell-specific enhancers are activated in the late stage in parallel with cell fate transition. Both epigenetic remodeling and Oct4 binding contribute to the hyperdynamic enhancer signature transitions. The hierarchical Oct4 bindings are associated with distinct functional themes at different stages. Collectively, our results provide a comprehensive molecular roadmap of Oct4 binding in concert with epigenetic rearrangements and rich resources for future reprogramming studies.