Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3.

In mammalian genomes, differentially methylated regions (DMRs) and histone marks including trimethylation of histone 3 lysine 27 (H3K27me3) at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. However, neither parent-of-origin-specific transcription nor imprints have been comprehensively mapped at the blastocyst stage of preimplantation development. Here, we address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos. We find that seventy-one genes exhibit previously unreported parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expressed). Uniparental expression of nBiX genes disappears soon after implantation. Micro-whole-genome bisulfite sequencing (µWGBS) of individual uniparental blastocysts detects 859 DMRs. We further find that 16% of nBiX genes are associated with a DMR, whereas most are associated with parentally-biased H3K27me3, suggesting a role for Polycomb-mediated imprinting in blastocysts. nBiX genes are clustered: five clusters contained at least one published imprinted gene, and five clusters exclusively contained nBiX genes. These data suggest that early development undergoes a complex program of stage-specific imprinting involving different tiers of regulation

Cooperative genetic networks drive embryonic stem cell transition from naïve to formative pluripotency.

In the mammalian embryo, epiblast cells must exit the naïve state and acquire formative pluripotency. This cell state transition is recapitulated by mouse embryonic stem cells (ESCs), which undergo pluripotency progression in defined conditions in vitro. However, our understanding of the molecular cascades and gene networks involved in the exit from naïve pluripotency remains fragmentary. Here, we employed a combination of genetic screens in haploid ESCs, CRISPR/Cas9 gene disruption, large-scale transcriptomics and computational systems biology to delineate the regulatory circuits governing naïve state exit. Transcriptome profiles for 73 ESC lines deficient for regulators of the exit from naïve pluripotency predominantly manifest delays on the trajectory from naïve to formative epiblast. We find that gene networks operative in ESCs are also active during transition from pre- to post-implantation epiblast in utero. We identified 496 naïve state-associated genes tightly connected to the in vivo epiblast state transition and largely conserved in primate embryos. Integrated analysis of mutant transcriptomes revealed funnelling of multiple gene activities into discrete regulatory modules. Finally, we delineate how intersections with signalling pathways direct this pivotal mammalian cell state transition

Human affective response to cooking fire odor

Die attraktive Wirkung des Grillens auf Männer scheint transkulturell bekannt zu sein, bisher wurde diese Beobachtung jedoch nicht wissenschaftlich untersucht. Der Grill könnte als urbane Art eines Lagerfeuers betrachtet werden. Die Kontrolle über das Feuer hat die Evolution des Menschen maßgeblich geprägt; sie brachte wesentlichen Nutzen, wie Wärme, Licht, Schutz gegen Raubtiere und das Kochen. Neben der direkten Gefahr stellt Feuer auch aufgrund der toxischen Bestandteile des Rauchs eine Bedrohung dar. Diese ist die erste Studie, die sich mit der emotionalen Reaktion auf Kochfeuer-Gerüche beschäftigt und hat zum Ziel diese zu beschreiben. Zusätzlich stellten wir unter Betracht der Theorie des ungleichen parentalen Investments, nach der Frauen die potentielle Gefahr Feuer eher meiden sollten als Männer, folgende Hypothese auf: Im Vergleich zu Männern werden Frauen auf Feuergeruch mit abstoßenden Gefühlen höherer Intensität reagieren. Unter Einsatz der Methode “Emotion and Odor Scale” beschrieben 105 junge Erwachsene ihre durch Gerüche hervorgerufenen Gefühle. Fünf verschiedene Geruchsstimuli von Feuerrauch wurden in Form von „Sniffin‘ Sticks“ eingesetzt. Die Probanden zeigten positive Reaktionen darauf und Frauen berichteten stärkere Gefühle des Wohlbefindens bei der Wahrnehmung eines bestimmten Raucharomas. Frauen reagierten jedoch ambivalent und empfanden durch zwei der Aromen mehr Ekel als Männer. Der Fragebogen ergab eine stärkere Anziehung von Feuer auf Männer. Die Ergebnisse unterstützen die Theorie, dass Frauen olfaktorische Anpassungen entwickelt haben, die zu sensibleren Reaktionen auf Feuergerüche führen. Im Einklang mit der kritischen Rolle des Feuers in unserer Evolution unterstreicht die Studie die Komplexität der emotionalen Reaktion auf Feuer.The attraction of men to barbecue grills seems spread cross-culturally, but it has never been approached scientifically. The barbecue grill might be viewed as the urban version of a campfire. The control of fire has shaped human evolution substantially by providing warmth, light, scaring away predators and enabling cooking. However, aside from the direct threat of the heat, fire represents a potential hazard due to toxic chemical compounds in fire smoke. In this study, the affective emotional response to olfactory stimuli of cooking fire smoke flavors is tested for the first time. In addition to the descriptive approach, we hypothesized that women should avoid fire as a potential hazard rather than men, considering the theory of unequal parental investment. Thus, fire odor should evoke stronger repellent feelings in women. Via the method “Emotion and Odor Scale” 105 normosmic young adults rated their emotions evoked by odor stimuli. Five different fire odor samples were presented in the form of “Sniffin’ Sticks”. Participants responded towards fire smoke odors with positive feelings and women responded to a particular odor with increased feelings of well-being. However, women showed ambivalent emotions, as they felt more disgusted by two smoke odors. Men reported stronger attraction to fire than women. These findings support the idea that women have evolved olfactory functions, which lead to more sensitive affective response to fire. Our study emphasizes the complexity of human affective response to fire in accordance with its critical role in human evolution

The painted gut

Die Ursachen für chronisch entzündliche Darmerkrankungen, wie Morbus Crohn und Colitis ulcerosa, sind weitgehend ungeklärt. Neben genetischen Veranlagungen werden Veränderungen in der Zusammensetzung der Darm-Mikrobiota mit den Erkrankungen in Verbindung gebracht. Dabei kann ein Verlust an potentiell gesundheitsfördernden Mikroorganismen beobachtet werden, während die Anzahl an opportunistischen Pathogenen steigt. Fluoreszenz in situ Hybridisierung (FISH) stellt eine ideale Methode dar um die Häufigkeit derjenigen Mikroorganismen zu bestimmen, die als „intestinale mikrobielle Biomarker“ Aufschluss über den Gesundheitszustand geben können. Ziel dieser Studie war Veränderungen in der Häufigkeit bestimmter mikrobieller Indikator-Spezies in verschiedenen Maus Entzündungsmodellen zu untersuchen. Hierfür wurden neue 16S rRNA-gerichtete FISH-Sonden für den spezifischen Nachweis von 13 abundanten, zum Teil unkultivierten Bakterienarten der Darm-Mikrobiota von Mäusen entwickelt. Die Sonden wurden unter Verwendung mehrerer Methoden systematisch evaluiert. Anschließend wurden drei dieser neu entwickelten Sonden exemplarisch eingesetzt um Veränderungen in der relativen Häufigkeit unkultivierter Arten der Ordnung Bacteroidales über den Verlauf einer Kolitis – von Induktion bis Auflösung der Entzündung – zu bestimmen. Des Weiteren wurden durch den erfolgreichen Einsatz zweier für FISH untypischer Fluorophore erste Erfolge in Richtung der Entwicklung eines neuen multiplex FISH Ansatzes erzielt. Abschließend wurde eine umfassende Liste von bisher publizierten FISH-Sonden für den Nachweis der intestinalen Mikrobiota von Mensch und Tier zusammengestellt und in der Internet-Datenbank probeBase veröffentlicht.Inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis are characterized by chronic intestinal inflammation of largely unknown causes. In addition to genetic risk factors that predispose individuals to IBD, the composition of the intestinal microbiota is altered in disease, resulting in the loss of beneficial microbes and increase in opportunistic pathogens. Fluorescence in situ hybridization (FISH) is an ideal method for monitoring the abundance of intestinal microorganisms that can serve as health-state biomarkers. This study aimed to illuminate the abundance shifts and possible role of the microbiota in mouse models of intestinal inflammation, but a suitable set of oligonucleotide probes to target abundant microorganisms has been limited. 16S rRNA gene-targeted FISH probes were developed that are specific for 13 bacterial species-level phylotypes in the mouse gut. The probes were systematically evaluated using multiple approaches. As a proof-of-concept, three newly-designed probes targeting phylotypes within an as-yet completely uncultivable group from the order Bacteroidales were applied to monitor abundance shifts throughout inflammation induction and resolution. The idea of developing a contemporary multiplex FISH approach using mono-labeled probes resulted in the successful application of two fluorophores that are unusual for FISH. Additionally, a comprehensive list of published FISH probes targeting the intestinal microbiota of humans and animals was created

Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3

Abstract: In mammalian genomes, differentially methylated regions (DMRs) and histone marks including trimethylation of histone 3 lysine 27 (H3K27me3) at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. However, neither parent-of-origin-specific transcription nor imprints have been comprehensively mapped at the blastocyst stage of preimplantation development. Here, we address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos. We find that seventy-one genes exhibit previously unreported parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expressed). Uniparental expression of nBiX genes disappears soon after implantation. Micro-whole-genome bisulfite sequencing (µWGBS) of individual uniparental blastocysts detects 859 DMRs. We further find that 16% of nBiX genes are associated with a DMR, whereas most are associated with parentally-biased H3K27me3, suggesting a role for Polycomb-mediated imprinting in blastocysts. nBiX genes are clustered: five clusters contained at least one published imprinted gene, and five clusters exclusively contained nBiX genes. These data suggest that early development undergoes a complex program of stage-specific imprinting involving different tiers of regulation

Novel imprints in mouse blastocysts are predominantly DNA methylation independent

In mammals, chromatin marks at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. This control is thought predominantly to involve parent-specific differentially methylated regions (DMR) in genomic DNA. However, neither parent-of-origin-specific transcription nor DMRs have been comprehensively mapped. We here address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos (blastocysts). Transcriptome-analysis identified 71 genes expressed with previously unknown parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expression). Uniparental expression of nBiX genes disappeared soon after implantation. Micro-whole-genome bisulfite sequencing (μWGBS) of individual uniparental blastocysts detected 859 DMRs. Only 18% of nBiXs were associated with a DMR, whereas 60% were associated with parentally-biased H3K27me3. This suggests a major role for Polycomb-mediated imprinting in blastocysts. Five nBiX-clusters contained at least one known imprinted gene, and five novel clusters contained exclusively nBiX-genes. These data suggest a complex program of stage-specific imprinting involving different tiers of regulation

NMD is required for timely cell fate transitions by fine-tuning gene expression and regulating translation

Cell fate transitions depend on balanced rewiring of transcription and translation programs to mediate ordered developmental progression. Components of the nonsense-mediated mRNA decay (NMD) pathway have been implicated in regulating embryonic stem cell (ESC) differentiation, but the exact mechanism is unclear. Here we show that NMD controls expression levels of the translation initiation factor Eif4a2 and its premature termination codon-encoding isoform (Eif4a2(PTC)). NMD deficiency leads to translation of the truncated eIF4A2(PTC) protein. eIF4A2(PTC) elicits increased mTORC1 activity and translation rates and causes differentiation delays. This establishes a previously unknown feedback loop between NMD and translation initiation. Furthermore, our results show a clear hierarchy in the severity of target deregulation and differentiation phenotypes between NMD effector KOs (Smg5 KO > Smg6 KO > Smg7 KO), which highlights heterodimer-independent functions for SMG5 and SMG7. Together, our findings expose an intricate link between mRNA homeostasis and mTORC1 activity that must be maintained for normal dynamics of cell state transitions