Designing signaling environments to steer transcriptional diversity in neural progenitor cell populations

Stem cell populations within developing embryos are diverse, composed of many different subpopulations of cells with varying developmental potential. The structure of stem cell populations in cell culture remains poorly understood and presents a barrier to differentiating stem cells for therapeutic applications. In this paper we develop a framework for controlling the architecture of stem cell populations in cell culture using high-throughput single cell mRNA-seq and computational analysis. We find that the transcriptional diversity of neural stem cell populations collapses in cell culture. Cell populations are depleted of committed neuron progenitor cells and become dominated by a single pre-astrocytic cell population. By analyzing the response of neural stem cell populations to forty distinct signaling conditions, we demonstrate that signaling environments can restructure cell populations by modulating the relative abundance of pre-astrocyte and pre-neuron subpopulations according to a simple linear code. One specific combination of BMP4, EGF, and FGF2 ligands switches the default population balance such that 70% of cells correspond to the committed neurons. Our work demonstrates that single-cell RNA-seq can be applied to modulate the diversity of in vitro stem cell populations providing a new strategy for population-level stem cell control

Designing signaling environments to steer transcriptional diversity in neural progenitor cell populations

Stem cell populations within developing embryos are diverse, composed of many different subpopulations of cells with varying developmental potential. The structure of stem cell populations in cell culture remains poorly understood and presents a barrier to differentiating stem cells for therapeutic applications. In this paper we develop a framework for controlling the architecture of stem cell populations in cell culture using high-throughput single cell mRNA-seq and computational analysis. We find that the transcriptional diversity of neural stem cell populations collapses in cell culture. Cell populations are depleted of committed neuron progenitor cells and become dominated by a single pre-astrocytic cell population. By analyzing the response of neural stem cell populations to forty distinct signaling conditions, we demonstrate that signaling environments can restructure cell populations by modulating the relative abundance of pre-astrocyte and pre-neuron subpopulations according to a simple linear code. One specific combination of BMP4, EGF, and FGF2 ligands switches the default population balance such that 70% of cells correspond to the committed neurons. Our work demonstrates that single-cell RNA-seq can be applied to modulate the diversity of in vitro stem cell populations providing a new strategy for population-level stem cell control

Dissecting heterogeneous cell populations across drug and disease conditions with PopAlign

Single-cell measurement techniques can now probe gene expression in heterogeneous cell populations from the human body across a range of environmental and physiological conditions. However, new mathematical and computational methods are required to represent and analyze gene expression changes that occur in complex mixtures of single cells as they respond to signals, drugs, or disease states. Here, we introduce a mathematical modeling platform, PopAlign, that automatically identifies subpopulations of cells within a heterogeneous mixture, and tracks gene expression and cell abundance changes across subpopulations by constructing and comparing probabilistic models. We apply PopAlign to analyze the impact of 42 different immunomodulatory compounds on a heterogeneous population of donor-derived human immune cells as well as patient-specific disease signatures in multiple myeloma. PopAlign scales to comparisons involving tens to hundreds of samples, enabling large-scale studies of natural and engineered cell populations as they respond to drugs, signals or physiological change

Bifaces acheuléens de Troussencourt

Rivaud C., Rivaud Jean Paul. Bifaces acheuléens de Troussencourt. In: Revue archéologique de l'Oise, n°4, 1973. Archéologie. Résurrection des habitats antiques dans l'Oise. pp. 21-22

Le gisement préhistorique d'Aux-Marais (Oise)

Rivaud Jean Paul. Le gisement préhistorique d'Aux-Marais (Oise). In: Revue archéologique de l'Oise, n°10, 1977. pp. 11-17

Home spirometry in bronchiolitis obliterans after allogeneic haematopoietic cell transplant

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Recherches Les modalités d’application du bilan de santé de la PAC sur le territoire national étaient précisées en février 2009. Quel sera l’impact économique des mesures adoptées ? Un outil statistique est mobilisé pour une simulation des effets redistributifs en termes d’aides directes et de revenus. Les politiques agro-environnementales impliquent une modification des savoir-faire. Comment les agriculteurs vont-ils s’approprier les différentes innovations environnementales ? Quelles sont les méthodes les plus couramment employées pour mesurer l’impact des projets de développement agricole ? Une méthode d’évaluation systémique est appliquée au cas d’un projet en République de Guinée. Les organisations de producteurs au Costa Rica se renforcent de plus en plus. Une pluralité des trajectoires apparaît donne lieu à une typologie nécessaire pour comprendre la construction de programmes d’appui dans un environnement institutionnel favorable à leur développement. Débats Comment informer les consommateurs ? Un dilemme pour le Parlement européen La fiscalité du bénéfice réel agricole est-elle encore efficace au regard des exigences économique, sociale et environnementale ? Faits et Chiffres La part croissante du salariat agricole Note de lecture 1960-2010 : panorama de la France rural

Commensal bacteria promote type I interferon signaling to maintain immune tolerance in mice

Type I interferons (IFNs) exert a broad range of biological effects important in coordinating immune responses, which have classically been studied in the context of pathogen clearance. Yet, whether immunomodulatory bacteria operate through IFN pathways to support intestinal immune tolerance remains elusive. Here, we reveal that the commensal bacterium, Bacteroides fragilis, utilizes canonical antiviral pathways to modulate intestinal dendritic cells (DCs) and regulatory T cell (Treg) responses. Specifically, IFN signaling is required for commensal-induced tolerance as IFNAR1-deficient DCs display blunted IL-10 and IL-27 production in response to B. fragilis. We further establish that IFN-driven IL-27 in DCs is critical in shaping the ensuing Foxp3+ Treg via IL-27Rα signaling. Consistent with these findings, single-cell RNA sequencing of gut Tregs demonstrated that colonization with B. fragilis promotes a distinct IFN gene signature in Foxp3+ Tregs during intestinal inflammation. Altogether, our findings demonstrate a critical role of commensal-mediated immune tolerance via tonic type I IFN signaling

The −KTS splice variant of WT1 is essential for ovarian determination in mice

IMPORTANT , l'article est en accès libre, le lien est sur le site http://ibv.unice.fr/research-team/chaboissier/ , il est surligné si on utilise Google Chrome http://ibv.unice.fr/research-team/chaboissier/#:~:text=https%3A//www.science.org/stoken/author%2Dtokens/ST%2D1527/fullInternational audienceSex determination in mammals depends on the differentiation of the supporting lineage of the gonads into Sertoli or pregranulosa cells that govern testis and ovary development, respectively. Although the Y-linked testis-determining gene Sry has been identified, the ovarian-determining factor remains unknown. In this study, we identified −KTS, a major, alternatively spliced isoform of the Wilms tumor suppressor WT1, as a key determinant of female sex determination. Loss of − KTS variants blocked gonadal differentiation in mice, whereas increased expression, as found in Frasier syndrome, induced precocious differentiation of ovaries independently of their genetic sex. In XY embryos, this antagonized Sry expression, resulting in male-to-female sex reversal. Our results identify −KTS as an ovarian-determining factor and demonstrate that its time of activation is critical in gonadal sex differentiation