Reconstructing and Reprogramming the Tumor-Propagating Potential of Glioblastoma Stem-like Cells

Developmental fate decisions are dictated by master transcription factors (TFs) that interact with cis-regulatory elements to direct transcriptional programs. Certain malignant tumors may also depend on cellular hierarchies reminiscent of normal development but superimposed on underlying genetic aberrations. In glioblastoma (GBM), a subset of stem-like tumor-propagating cells (TPCs) appears to drive tumor progression and underlie therapeutic resistance, yet remain poorly understood. Here, we identify a core set of neurodevelopmental TFs (POU3F2, SOX2, SALL2, OLIG2) essential for GBM propagation. These TFs coordinately bind and activate TPC-specific regulatory elements, and are sufficient to fully reprogram differentiated GBM cells to ‘induced’ TPCs, recapitulating the epigenetic landscape and phenotype of native TPCs. We reconstruct a network model that highlights critical interactions and identifies novel therapeutic targets for eliminating TPCs. Our study establishes the epigenetic basis of a developmental hierarchy in GBM, provides detailed insight into underlying gene regulatory programs, and suggests attendant therapeutic strategies

Genetic and Epigenetic Fine-Mapping of Causal Autoimmune Disease Variants

Summary Genome-wide association studies have identified loci underlying human diseases, but the causal nucleotide changes and mechanisms remain largely unknown. Here we developed a fine-mapping algorithm to identify candidate causal variants for 21 autoimmune diseases from genotyping data. We integrated these predictions with transcription and cis-regulatory element annotations, derived by mapping RNA and chromatin in primary immune cells, including resting and stimulated CD4+ T-cell subsets, regulatory T-cells, CD8+ T-cells, B-cells, and monocytes. We find that ~90% of causal variants are noncoding, with ~60% mapping to immune-cell enhancers, many of which gain histone acetylation and transcribe enhancer-associated RNA upon immune stimulation. Causal variants tend to occur near binding sites for master regulators of immune differentiation and stimulus-dependent gene activation, but only 10–20% directly alter recognizable transcription factor binding motifs. Rather, most noncoding risk variants, including those that alter gene expression, affect non-canonical sequence determinants not well-explained by current gene regulatory models

La cultura popular y la represión de la élite en la Europa moderna temprana. Historias. Revista de la Dirección de Estudios Históricos. Num. 28 (1992) abril-septiembre

1 Max Weber: La ética protestante y el espíritu del capitalismo, Barcelona, 1988; Henry Kamen: The Iron Century: Social Change in Europe, 1550-1660, Nueva York, 1971, pp. 84-89 (trad. El siglo de hierro. Cambio social en Europa, 1550-1660, Alianza editorial, Madrid, 1977).2 Arnold van Gennep: Les rites de passage, Mouton & Co y Maison des Sciences de l'Homme, Suiza, 1969 (1909, 1a. ed). Mijail Bajtin: La cultura popular en la Edad Media y Renacimiento, Barral editores, Barcelona, 1971.3 Michel Foucault: Vigilar y castigar: Nacimiento de la prisión, Siglo XXI editores, México, 1976.4 Robert Mandrou: De la culture populaire aux XVII et XVIII siècles. La bibliothèque bleue de Troyes, Stock, París, 1964.5 Ives-Marie Bercé: Fête et révolte. Des mentalités populaires du XVI au XVIII siècles, Librairie Hachette, París, 1976.6 Keith, Thomas: Religion & the Decline of Magic, Charles Scribner's Sons, Nueva York, 1971; Jean Delumeau: Le Catholicisme entre Luther et Voltaire, Presses Universitaires de France, París, 1971; John Bossy: "The Counter-Reformation and the People of Catholic Europe", en Past & Present, 47 (1970), pp. 51-70; Natalie Zemon Davis: "Some Tasks and Themes in the Study of Popular Religion", en Charles Trinkhaus, ed.: The Pursuit of Holiness in Late Medieval and Renaissance Religion, Leiden, 1974, pp. 307-336.Reseñas a Peter Burke: Popular Culture in Early Modern Europe, New York University Press, Nueva York, 1978, y a Robert Muchembled: Culture populaire et culture des élites dans la France modeme, XVe-XVIIIe siècles: essai, Flammarion, París, 1978. Tomado de Journal of Interdisciplinary History, XI (1), verano de 1980, pp. 97-103

État et société en France au XVIIe siècle. La taille en Languedoc et la question de la redistribution sociale

State and Society in Seventeenth-Century France. Taxation in Languedoc and the Question of Social Distribution. The rise of the French state is often analyzed in terms of its ability to extract taxes from the population, especially in the seventeenth century, when figures for the taille become relatively reliable. However these figures, usually drawn from the work of J. R. Mallet, require close scrutiny. Mallet's figures, representing net revenues to the crown, do not tell us how much money was spent by the king in the provinces without ever reaching the treasury or how much was redistributed to local notables, and his figures for the "pays d'états" are incomplete. This article attempts to set the record straight for Languedoc. It establishes the total amount imposed on the province each year form 1628 to 1686 by the Estates, criticizes Mallet on the basis of this information, and analyzes where the money went in 1647 and 1677. It argues for a social interpretation of the relationship between state and society in which the state is viewed as distributor of wealth to the provincial elites and not merely as a centralizer of resources and power.Beik William, Guery Alain. État et société en France au XVIIe siècle. La taille en Languedoc et la question de la redistribution sociale. In: Annales. Économies, Sociétés, Civilisations. 39ᵉ année, N. 6, 1984. pp. 1270-1298