Electrospun bioresorbable polymer membranes for coronary artery stents.

Percutaneous coronary intervention, a common treatment for atherosclerotic coronary artery lesions, occasionally results in perforations associated with increased mortality rates. Stents coated with a bioresorbable polymer membrane may offer an effective solution for sealing coronary artery perforations. Additionally, such coatings could be effective in mitigating neointimal hyperplasia within the vascular lumen and correcting symptomatic aneurysms. This study examines polymer membranes fabricated by electrospinning of polycaprolactone, polydioxanone, polylactide-co-caprolactone, and polylactide-co-glycolide. In uniaxial tensile tests, all the materials appear to surpass theoretically derived elongation thresholds necessary for stent deployment, albeit polydioxanone membranes are found to disintegrate during the experimental balloon expansion. As revealed by in vitro hemocompatibility testing, polylactide-co-caprolactone membranes exhibit higher thrombogenicity compared to other evaluated polymers, while polylactide-co-glycolide samples fail within the first day post-implantation into the abdominal aorta in rats. The PCL membrane exhibited significant water leakage in the permeability test. Comprehensive evaluation of mechanical testing, bio- and hemocompatibility, as well as biodegradation dynamics shows the advantage of membranes based on and the mixture of polylactide-co-caprolactone and polydioxanone over other polymer groups. These findings lay a foundational framework for conducting preclinical studies on stent configurations in large laboratory animals, emphasizing that further investigations under conditions closely mimicking clinical use are imperative for making definitive conclusions.

The activity of early-life gene regulatory elements is hijacked in aging through pervasive AP-1-linked chromatin opening.

A mechanistic connection between aging and development is largely unexplored. Through profiling age-related chromatin and transcriptional changes across 22 murine cell types, analyzed alongside previous mouse and human organismal maturation datasets, we uncovered a transcription factor binding site (TFBS) signature common to both processes. Early-life candidate cis-regulatory elements (cCREs), progressively losing accessibility during maturation and aging, are enriched for cell-type identity TFBSs. Conversely, cCREs gaining accessibility throughout life have a lower abundance of cell identity TFBSs but elevated activator protein 1 (AP-1) levels. We implicate TF redistribution toward these AP-1 TFBS-rich cCREs, in synergy with mild downregulation of cell identity TFs, as driving early-life cCRE accessibility loss and altering developmental and metabolic gene expression. Such remodeling can be triggered by elevating AP-1 or depleting repressive H3K27me3. We propose that AP-1-linked chromatin opening drives organismal maturation by disrupting cell identity TFBS-rich cCREs, thereby reprogramming transcriptome and cell function, a mechanism hijacked in aging through ongoing chromatin opening.

Rhodobacteraceae are key players in microbiome assembly of the diatom Asterionellopsis glacialis.

The complex interactions between bacterioplankton and phytoplankton have prompted numerous studies that investigate phytoplankton microbiomes with the aim of characterizing beneficial or opportunistic taxa and elucidating core bacterial members. Oftentimes, this knowledge is garnered through 16S rRNA gene profiling of microbiomes from phytoplankton isolated across spatial and temporal scales, yet these studies do not offer insight into microbiome assembly and structuring. In this study, we aimed to identify taxa central to structuring and establishing the microbiome of the ubiquitous diatom Asterionellopsis glacialis. We introduced a diverse environmental bacterial community to A. glacialis in nutrient-rich or nutrient-poor media in a continuous dilution culture setup and profiled the bacterial community over 7 days. 16S rRNA amplicon sequencing showed that cyanobacteria (Coleofasciculaceae) and Rhodobacteraceae dominate the microbiome early on and maintain a persistent association throughout the experiment. Differential abundance, co-abundance networks, and differential association analyses revealed that specific members of the family Rhodobacteraceae, particularly Sulfitobacter amplicon sequence variants, become integral members in microbiome assembly. In the presence of the diatom, Sulfitobacter species and other Rhodobacteraceae developed positive associations with taxa that are typically in high abundance in marine ecosystems (Pelagibacter and Synechococcus), leading to restructuring of the microbiome compared to diatom-free controls. These positive associations developed predominantly under oligotrophic conditions, highlighting the importance of investigating phytoplankton microbiomes in as close to natural conditions as possible to avoid biases that develop under routine laboratory conditions. These findings offer further insight into phytoplankton-bacteria interactions and illustrate the importance of Rhodobacteraceae, not merely as phytoplankton symbionts but as key taxa involved in microbiome assembly. IMPORTANCE: Most, if not all, microeukaryotic organisms harbor an associated microbial community, termed the microbiome. The microscale interactions that occur between these partners have global-scale consequences, influencing marine primary productivity, carbon cycling, and harmful algal blooms to name but a few. Over the last decade, there has been a growing interest in the study of phytoplankton microbiomes, particularly within the context of bloom dynamics. However, long-standing questions remain regarding the process of phytoplankton microbiome assembly. The significance of our research is to tease apart the mechanism of microbiome assembly with a particular focus on identifying bacterial taxa, which may not merely be symbionts but architects of the phytoplankton microbiome. Our results strengthen the understanding of the ecological mechanisms that underpin phytoplankton-bacteria interactions in order to accurately predict marine ecosystem responses to environmental perturbations.

SinoNasal Microbiota Transfer to treat recalcitrant chronic rhinosinusitis: A case series.

KEY POINTS: SinoNasal Microbiota Transfer (SNMT) was safe with immediate benefit in all recipients, with sustained improvement in two of three recipients for up to 180 days. The addition of antimicrobial photodynamic therapy worsened chronic rhinosinusitis. These promising SNMT results warrant further study of safety and efficacy.

The coral microbiome in sickness, in health and in a changing world.

Stony corals, the engines and engineers of reef ecosystems, face unprecedented threats from anthropogenic environmental change. Corals are holobionts that comprise the cnidarian animal host and a diverse community of bacteria, archaea, viruses and eukaryotic microorganisms. Recent research shows that the bacterial microbiome has a pivotal role in coral biology. A healthy bacterial assemblage contributes to nutrient cycling and stress resilience, but pollution, overfishing and climate change can break down these symbiotic relationships, which results in disease, bleaching and, ultimately, coral death. Although progress has been made in characterizing the spatial-temporal diversity of bacteria, we are only beginning to appreciate their functional contribution. In this Review, we summarize the ecological and metabolic interactions between bacteria and other holobiont members, highlight the biotic and abiotic factors influencing the structure of bacterial communities and discuss the impact of climate change on these communities and their coral hosts. We emphasize how microbiome-based interventions can help to decipher key mechanisms underpinning coral health and promote reef resilience. Finally, we explore how recent technological developments may be harnessed to address some of the most pressing challenges in coral microbiology, providing a road map for future research in this field.

Molecular mechanisms of microbiome modulation by the eukaryotic secondary metabolite azelaic acid.

Photosynthetic eukaryotes, such as microalgae and plants, foster fundamentally important relationships with their microbiome based on the reciprocal exchange of chemical currencies. Among these, the dicarboxylate metabolite azelaic acid (Aze) appears to play an important, but heterogeneous, role in modulating these microbiomes, as it is used as a carbon source for some heterotrophs but is toxic to others. However, the ability of Aze to promote or inhibit growth, as well as its uptake and assimilation mechanisms into bacterial cells are mostly unknown. Here, we use transcriptomics, transcriptional factor coexpression networks, uptake experiments, and metabolomics to unravel the uptake, catabolism, and toxicity of Aze on two microalgal-associated bacteria, Phycobacter and Alteromonas, whose growth is promoted or inhibited by Aze, respectively. We identify the first putative Aze transporter in bacteria, a 'C4-TRAP transporter', and show that Aze is assimilated through fatty acid degradation, with further catabolism occurring through the glyoxylate and butanoate metabolism pathways when used as a carbon source. Phycobacter took up Aze at an initial uptake rate of 3.8×10-9 nmol/cell/hr and utilized it as a carbon source in concentrations ranging from 10 µM to 1 mM, suggesting a broad range of acclimation to Aze availability. For growth-impeded bacteria, we infer that Aze inhibits the ribosome and/or protein synthesis and that a suite of efflux pumps is utilized to shuttle Aze outside the cytoplasm. We demonstrate that seawater amended with Aze becomes enriched in bacterial families that can catabolize Aze, which appears to be a different mechanism from that in soil, where modulation by the host plant is required. This study enhances our understanding of carbon cycling in the oceans and how microscale chemical interactions can structure marine microbial populations. In addition, our findings unravel the role of a key chemical currency in the modulation of eukaryote-microbiome interactions across diverse ecosystems.

"A comparison of thermal stress response between Drosophila melanogaster and Drosophila pseudoobscura reveals differences between species and sexes".

The environment is changing faster than anticipated due to climate change, making species more vulnerable to its impacts. The level of vulnerability of species is influenced by factors such as the degree and duration of exposure, as well as the physiological sensitivity of organisms to changes in their environments, which has been shown to vary among species, populations, and individuals. Here, we compared physiological changes in fecundity, critical thermalmaximum (CTmax), respiratory quotient (RQ), and DNA damage in ovaries in response to temperature stress in two species of fruit fly, Drosophila melanogaster (25 vs. 29.5 °C) and Drosophila pseudoobscura (20.5 vs. 25 °C). The fecundity of D. melanogaster was more affected by high temperatures when exposed during egg through adult development, while D. pseudoobscura was most significantly affected when exposed to high temperatures exclusively during egg through pupal development. Additionally, D. melanogaster males exhibited a decrease of CTmax under high temperatures, while females showed an increase of CTmax when exposed to high temperatures during egg through adult development. while D. pseudoobscura females and males showed an increased CTmax only when reared at high temperatures during egg through pupae development. Moreover, both species showed an acceleration in oogenesis and an increase in apoptosis due to heat stress. These changes can likely be attributed to key differences in the geographic range, thermal range, development time, and other different factors between these two systems. Through this comparison of variation in physiology and developmental response to thermal stress, we found important differences between species and sexes that suggest future work needs to account for these factors separately in understanding the effects of constant increased temperatures.

Insights on hexavalent chromium(VI) remediation strategies in abiotic and biotic dual chamber microbial fuel cells: electrochemical, physical, and metagenomics characterizations.

Hexavalent chromium [Cr(VI)] is one of the most carcinogenic and mutagenic toxins, and is commonly released into the environemt from different industries, including leather tanning, pulp and paper manufacturing, and metal finishing. This study aimed to investigate the performance of dual chamber microbial fuel cells (DMFCs) equipped with a biocathode as alternative promising remediation approaches for the biological reduction of hexavalent chromium [Cr(VI)] with instantaneous power generation. A succession batch under preliminary diverse concentrations of Cr(VI) (from 5 to 60 mg L-1) was conducted to investigate the reduction mechanism of DMFCs. Compared to abiotic-cathode DMFC, biotic-cathode DMFC exhibited a much higher power density, Cr(VI) reduction, and coulombic efficiency over a wide range of Cr(VI) concentrations (i.e., 5-60 mg L-1). Furthermore, the X-ray photoelectron spectroscopy (XPS) revealed that the chemical functional groups on the surface of biotic cathode DMFC were mainly trivalent chromium (Cr(III)). Additionally, high throughput sequencing showed that the predominant anodic bacterial phyla were Firmicutes, Proteobacteria, and Deinococcota with the dominance of Clostridiumsensu strict 1, Enterobacter, Pseudomonas, Clostridiumsensu strict 11 and Lysinibacillus in the cathodic microbial community. Collectively, our results showed that the Cr(VI) removal occurred through two different mechanisms: biosorption and bioelectrochemical reduction. These findings confirmed that the DMFC could be used as a bioremediation approach for the removal of Cr(VI) commonly found in different industrial wastewater, such as tannery effluents. with simultaneous bioenergy production.

A Comprehensive Study on Signal Transduction and Therapeutic Role of miR-877 in Human Cancers.

MicroRNAs are a group of short non-coding RNAs (miRNAs), which are epigenetically involved in gene expression and other cellular biological processes and can be considered as potential biomarkers for cancer detection and support for treatment management. This review aims to amass the evidence in order to reach the molecular mechanism and clinical significance of miR-877 in different types of cancer. Dysregulation of miR-877 level in various types of malignancies as bladder cancer, cervical cancer, cholangiocarcinoma, colorectal cancer (CRC), gastric cancer, glioblastoma, head and neck squamous cell carcinoma (HNSCC), hepatocellular carcinoma, laryngeal squamous cell carcinoma, melanoma, non-small cell lung cancer (NSCLC), oral squamous cell carcinoma, ovarian cancer (OC), pancreatic ductal adenocarcinoma, and renal cell carcinoma (RCC) have reported, significantly increase or decrease in its level, which can be indicated to its function as oncogene or tumor suppressor. MiR-877 is involved in cell proliferation, migration, and invasion through cell cycle pathways in cancer. MiR-877 could be potential a candidate as a valuable biomarker for prognosis in various cancers. Through this study, we proposed that miR-877 can potentially be a candidate as a prognostic marker for early detection of tumor development, progression, as well as metastasis.

Comparison of the Patency and Regenerative Potential of Biodegradable Vascular Prostheses of Different Polymer Compositions in an Ovine Model.

The lack of suitable autologous grafts and the impossibility of using synthetic prostheses for small artery reconstruction make it necessary to develop alternative efficient vascular grafts. In this study, we fabricated an electrospun biodegradable poly(ε-caprolactone) (PCL) prosthesis and poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(ε-caprolactone) (PHBV/PCL) prosthesis loaded with iloprost (a prostacyclin analog) as an antithrombotic drug and cationic amphiphile with antibacterial activity. The prostheses were characterized in terms of their drug release, mechanical properties, and hemocompatibility. We then compared the long-term patency and remodeling features of PCL and PHBV/PCL prostheses in a sheep carotid artery interposition model. The research findings verified that the drug coating of both types of prostheses improved their hemocompatibility and tensile strength. The 6-month primary patency of the PCL/Ilo/A prostheses was 50%, while all PHBV/PCL/Ilo/A implants were occluded at the same time point. The PCL/Ilo/A prostheses were completely endothelialized, in contrast to the PHBV/PCL/Ilo/A conduits, which had no endothelial cells on the inner layer. The polymeric material of both prostheses degraded and was replaced with neotissue containing smooth-muscle cells; macrophages; proteins of the extracellular matrix such as type I, III, and IV collagens; and vasa vasorum. Thus, the biodegradable PCL/Ilo/A prostheses demonstrate better regenerative potential than PHBV/PCL-based implants and are more suitable for clinical use.

Selenium-transition metal supported on a mixture of reduced graphene oxide and silica template for water splitting.

Exploration of economical, highly efficient, and environment friendly non-noble-metal-based electrocatalysts is necessary for hydrogen and oxygen evolution reactions (HER and OER) but challenging for cost-effective water splitting. Herein, metal selenium nanoparticles (M = Ni, Co & Fe) are anchored on the surface of reduced graphene oxide and a silica template (rGO-ST) through a simple one-pot solvothermal method. The resulting electrocatalyst composite can enhance mass/charge transfer and promote interaction between water molecules and electrocatalyst reactive sites. NiSe2/rGO-ST shows a remarkable overpotential (52.5 mV) at 10 mA cm-2 for the HER compared to the benchmark Pt/C E-TEK (29 mV), while the overpotential values of CoSeO3/rGO-ST and FeSe2/rGO-ST are 246 and 347 mV, respectively. The FeSe2/rGO-ST/NF shows a low overpotential (297 mV) at 50 mA cm-2 for the OER compared to RuO2/NF (325 mV), while the overpotentials of CoSeO3-rGO-ST/NF and NiSe2-rGO-ST/NF are 400 and 475 mV, respectively. Furthermore, all catalysts indicate negligible deterioration, indicating better stability during the process of HER and OER after a stability test of 60 h. The water splitting system composed of NiSe2-rGO-ST/NF||FeSe2-rGO-ST/NF electrodes requires only ∼1.75 V at 10 mA cm-2. Its performance is nearly close to that of a noble metal-based Pt/C/NF||RuO2/NF water splitting system.

The coral microbiome: towards an understanding of the molecular mechanisms of coral-microbiota interactions.

Corals live in a complex, multipartite symbiosis with diverse microbes across kingdoms, some of which are implicated in vital functions, such as those related to resilience against climate change. However, knowledge gaps and technical challenges limit our understanding of the nature and functional significance of complex symbiotic relationships within corals. Here, we provide an overview of the complexity of the coral microbiome focusing on taxonomic diversity and functions of well-studied and cryptic microbes. Mining the coral literature indicate that while corals collectively harbour a third of all marine bacterial phyla, known bacterial symbionts and antagonists of corals represent a minute fraction of this diversity and that these taxa cluster into select genera, suggesting selective evolutionary mechanisms enabled these bacteria to gain a niche within the holobiont. Recent advances in coral microbiome research aimed at leveraging microbiome manipulation to increase coral's fitness to help mitigate heat stress-related mortality are discussed. Then, insights into the potential mechanisms through which microbiota can communicate with and modify host responses are examined by describing known recognition patterns, potential microbially derived coral epigenome effector proteins and coral gene regulation. Finally, the power of omics tools used to study corals are highlighted with emphasis on an integrated host-microbiota multiomics framework to understand the underlying mechanisms during symbiosis and climate change-driven dysbiosis.

The Effects of Nasal Surgery on Pulmonary Function: A Systematic Review and Meta-Analysis.

OBJECTIVE: A deviated nasal septum (DNS) can result in an anatomical obstruction and impact lung function through prolonged suboptimal inspiration. Given the improvements in respiration reported by patients following septoplasty or septorhinoplasty (with or without inferior turbinate reduction), our study investigated the effect of these procedures on pulmonary function through a systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Cochrane Databases, Web of Science, and Google Scholar. REVIEW METHODS: The review was registered with PROSPERO [CRD42022316309]. The study population was composed of adult patients (18-65) who were symptomatic with confirmed DNS. Extracted outcomes (pre-operative versus postoperative) included the six-minute walk test (6MWT) and pulmonary function tests (FEV1, FVC, FEV1/FVC, FEF25-75, PEF). Meta-analyses were performed using a random-effects model. RESULTS: Three studies included measures of the 6MWT in meters and all three found a statistically significant increase in the distance walked after surgery with a mean difference of 62.40 m (95% CI 24.79-100.00). Statistically significant improvements in PFT outcomes were observed with a standard mean difference of 0.72 for FEV1 (95% CI 0.31-1.13), 0.63 for FVC (95% CI 0.26-1.00), and 0.64 for PEF (95% CI 0.47-0.82). Of the twelve studies which measured PFT outcomes, six showed statistically significant improvements, three studies showed mixed results, and three studies found no difference in PFT outcomes between pre-and post-surgery testing. CONCLUSIONS: The present study suggests that pulmonary function does improve after nasal surgery for DNS, but the high heterogeneity observed in the meta-analyses indicates that the evidence supporting this conclusion is low. Laryngoscope, 133:2837-2845, 2023.

Safety and efficacy of cobimetinib plus atezolizumab in patients with solid tumors: a phase II, open-label, multicenter, multicohort study.

BACKGROUND: Although introduction of immune checkpoint inhibitors has revolutionized the treatment of cancer, their response rates are generally low. Preclinical and early phase clinical data suggest that MEK inhibition may sensitize tumors to immune checkpoint inhibitors by upregulating tumor antigen expression, programmed death-ligand 1 (PD-L1) expression, and tumor T-cell infiltration. We evaluated the efficacy and safety of cobimetinib plus atezolizumab in patients with advanced solid tumors in the open-label, multicohort phase II COTEST study. PATIENTS AND METHODS: This analysis of the COTEST trial included patients from cohorts 1-4 [1-3: anti-programmed cell death protein 1 (PD-1)/PD-L1 treatment-naive patients; 4: patients with disease progression on anti-PD-1/anti-PD-L1 treatment] who received cobimetinib 60 mg once daily for the first 21 days and intravenous infusions of atezolizumab 840 mg on days 1 and 15 of each 28-day cycle. Efficacy endpoints included objective response rate, overall survival, progression-free survival (PFS), and disease control rate. RESULTS: Overall, 77 patients were enrolled in cohorts 1-4 (78% male; median age 62.8 years). Objective response rate was 20% in cohort 1 [squamous cell carcinoma of the head and neck (SCCHN)], 30% in cohort 2 (urothelial carcinoma), and 18% in cohort 3 (renal cell carcinoma); there were no responders among 20 patients in cohort 4 (SCCHN). The disease control rates in cohorts 1-4 were 50%, 40%, 24%, and 25%, respectively. The median PFS was 5.5, 3.4, 3.4, and 3.6 months in cohorts 1-4, respectively, and the median overall survival was 16.8, 18.7, 21.7, and 7.7 months, respectively. Most adverse events were of grade 1/2 and were manageable. CONCLUSIONS: Cobimetinib plus atezolizumab had moderate activity in patients with anti-PD-1/PD-L1 treatment-naive SCCHN and urothelial carcinoma, and weak activity in anti-PD-1/PD-L1 treatment-naive renal cell carcinoma, and no activity in checkpoint inhibitor-treated patients.

Ambulatory transcutaneous carbon dioxide monitoring for children with neuromuscular disease.

OBJECTIVE: Early screening and diagnosis of nocturnal hypoventilation can slow progression to diurnal hypercapnia and mortality in children with neuromuscular disease (NMD). However, gold standard, laboratory-based polysomnography (PSG) testing is a limited resource. Therefore, we evaluated the diagnostic accuracy of ambulatory transcutaneous carbon dioxide (tcCO2) monitoring used in the home compared to PSG in children with NMD. METHODS: Prospective, cross-sectional study in children 0-18 years old with a confirmed diagnosis of NMD and a clinically indicated need for PSG. Ambulatory tcCO2 was assessed by a respiratory therapist in participant's homes. Demographics, and PSG (including tcCO2). RESULTS: We enrolled 39 children with NMD; 3 had unusable ambulatory tcCO2 data because of failure of drift correction on the machine (n = 2) or an air bubble (n = 1). The remaining 36 patients aged 11 months to 16 years (median (IQR) 12.5 years (6.0-15.8)) had ambulatory tcCO2 and outpatient level 1 PSG data. Ambulatory tcCO2 monitoring had a sensitivity of 20.0% (95% confidence interval [CI] 0.5-71.6%) and a specificity of 93.5% (95% CI 78.6-99.2%). Almost all children and/or parents (34/36, 94%) preferred ambulatory monitoring over in-hospital PSG. CONCLUSIONS: Ambulatory transcutaneous carbon dioxide monitoring was not sufficiently accurate as a clinical tool for the diagnosis of nocturnal hypoventilation our cohort of children with neuromuscular disease despite being preferred over PSG by both children and parents.

Leveraging transcriptome and epigenome landscapes to infer regulatory networks during the onset of sexual maturation.

BACKGROUND: Despite sexual development being ubiquitous to vertebrates, the molecular mechanisms underpinning this fundamental transition remain largely undocumented in many organisms. We designed a time course experiment that successfully sampled the period when Atlantic salmon commence their trajectory towards sexual maturation. RESULTS: Through deep RNA sequencing, we discovered key genes and pathways associated with maturation in the pituitary-ovarian axis. Analyzing DNA methylomes revealed a bias towards hypermethylation in ovary that implicated maturation-related genes. Co-analysis of DNA methylome and gene expression changes revealed chromatin remodeling genes and key transcription factors were both significantly hypermethylated and upregulated in the ovary during the onset of maturation. We also observed changes in chromatin state landscapes that were strongly correlated with fundamental remodeling of gene expression in liver. Finally, a multiomic integrated analysis revealed regulatory networks and identified hub genes including TRIM25 gene (encoding the estrogen-responsive finger protein) as a putative key regulator in the pituitary that underwent a 60-fold change in connectivity during the transition to maturation. CONCLUSION: The study successfully documented transcriptome and epigenome changes that involved key genes and pathways acting in the pituitary - ovarian axis. Using a Systems Biology approach, we identified hub genes and their associated networks deemed crucial for onset of maturation. The results provide a comprehensive view of the spatiotemporal changes involved in a complex trait and opens the door to future efforts aiming to manipulate puberty in an economically important aquaculture species.

Esrrb Regulates Specific Feed-Forward Loops to Transit From Pluripotency Into Early Stages of Differentiation.

Characterization of pluripotent states, in which cells can both self-renew or differentiate, with the irreversible loss of pluripotency, are important research areas in developmental biology. Although microRNAs (miRNAs) have been shown to play a relevant role in cellular differentiation, the role of miRNAs integrated into gene regulatory networks and its dynamic changes during these early stages of embryonic stem cell (ESC) differentiation remain elusive. Here we describe the dynamic transcriptional regulatory circuitry of stem cells that incorporate protein-coding and miRNA genes based on miRNA array expression and quantitative sequencing of short transcripts upon the downregulation of the Estrogen Related Receptor Beta (Esrrb). The data reveals how Esrrb, a key stem cell transcription factor, regulates a specific stem cell miRNA expression program and integrates dynamic changes of feed-forward loops contributing to the early stages of cell differentiation upon its downregulation. Together these findings provide new insights on the architecture of the combined transcriptional post-transcriptional regulatory network in embryonic stem cells.