Single cell RNA sequencing to uncover intestinal cell-type specific cis-eQTL driving inherited predisposition to IBD

IBD is characterized by a chronic idiopathic inflammation of the gastrointestinal (GI) tract and consist of two main forms: ulcerative colitis and Crohn’s disease. The importance of genetic susceptibility has been well established through Genome Wide Association Studies (GWAS), which have identified over 200 risk loci for IBD. However, the « true causative » genes in these loci have been identified for only few on the basis of independently associated coding variants. Fine-mapping studies suggested that most risk variants cause “cis”-eQTL in disease relevant cell types, but recent post-GWAS studies could not find matching cis-eQTLs for the majority of risk loci (137/200). This indicates that the relevant cell types were either not present amongst the analyzed cell populations or under-represented. In this study, we performed cis-eQTL analysis with single cell RNA-seq of human gut biopsies to uncover the truly relevant cell types with higher resolution and unbiased approach. Biopsies were collected from three GI locations (ileum, transverse colon, rectum) from the same individuals. Cell suspensions were prepared, tagged by location and cell fraction using TotalseqB hashtag antibodies for multiplexing and processed to the 10X Genomics Chromium. Data were analyzed using Cellranger and Seurat to identify the cell clusters and marker genes. In total, 50 individuals’ biopsies data were integrated. Simultaneously, genotype was analyzed with Infinium OmniExpress-24v1 chip from 1 ml blood and imputed. Both scRNA-seq data and imputed genotypes were input to qtltools v1.3.1 for cis-eQTL anlaysis. Analysis are actually ongoing and will certainly generate new set of cell-based eQTL and determine whether some of these drive inherited predisposition to IBD by comparing the corresponding expression association patterns with disease association patterns using methods developed in our laboratory

Combined analysis of single cell RNA-Seq and ATAC-Seq data reveals putative regulatory toggles operating in native and iPS-derived retina.

We report the generation and analysis of single-cell RNA-Seq data (> 38,000 cells) from native and iPSC-derived murine retina at four matched developmental stages spanning the emergence of the major retinal cell types. We combine information from temporal sampling, visualization of 3D UMAP manifolds, pseudo-time and RNA velocity analyses, to show that iPSC-derived 3D retinal aggregates broadly recapitulate the native developmental trajectories. However, we show relaxation of spatial and temporal transcriptome control, premature emergence and dominance of photoreceptor precursor cells, and susceptibility of dynamically regulated pathways and transcription factors to culture conditions in iPSC-derived retina. We generate bulk ATAC-Seq data for native and iPSC-derived murine retina identifying ~125,000 peaks. We combine single-cell RNA-Seq with ATAC-Seq information and obtain evidence that approximately half the transcription factors that are dynamically regulated during retinal development may act as repressors rather than activators. We propose that sets of activators and repressors with cell-type specific expression constitute regulatory toggles that lock cells in distinct transcriptome states underlying differentiation. We provide evidence supporting our hypothesis from the analysis of publicly available single-cell ATAC-Seq data for adult mouse retina. We identify subtle but noteworthy differences in the operation of such toggles between native and iPSC-derived retina particularly for the Etv1, Etv5, Hes1 and Zbtb7a group of transcription factors

Diametral dimension(s) and prominent bounded sets

The classical diametral dimension (Bessaga, Mityagin, Pelczynski, Rolewicz), denoted by "Delta", is a topological invariant which can be used to characterize Schwartz and nuclear locally convex spaces. Mityagin also introduced a variant of this diametral dimension, denoted by "Delta_b", using bounded sets in its definition, contrary to "Delta". In this talk, we present some conditions assuring the equality of these two diametral dimensions for Fréchet spaces. Among these conditions, there is the notion of existence of prominent bounded sets, due to Terzioglu. In fact, it appears that the existence of prominent sets is implied by the property "Omega Bar" of Vogt and Wagner. Finally, we describe a construction which gives Schwartz and nuclear non-Fréchet spaces E verifying "Delta_b(E) = \Delta(E)"

Nombres premiers et cryptographie

Vulgarisation de l'emploi des nombres premiers en cryptographies (RSA), présentée dans le cadre du cours "Communiquer la Science" de Yaël Nazé (formation doctorale

Diametral dimensions and some applications to spaces Snu

The "classic" diametral dimension is a topological invariant which characterizes Schwartz and nuclear locally convex spaces. Besides, there exists a second diametral dimension which is conjectured to be equal to the first one (on Fréchet-Schwartz spaces). The first part of this thesis is dedicated to the study of this conjecture. We present several positive partial results in metrizable spaces (in particular in Köthe sequence spaces and Hilbertizable spaces) and some properties which provide the equality of the two diametral dimensions (such as the Delta-stability, the existence of prominent bounded sets, and the property Omega bar). Then, we describe the construction of some non-metrizable locally convex spaces for which the two diametral dimensions are different. The other purpose of this work is to pursue the topological study of sequence spaces Snu, originally defined in the context of multifractal analysis. For this, the second part of the present thesis focuses on the study of the two diametral dimensions in spaces Snu. Finally, we show that some classes of spaces Snu verify (a variation of) the property Omega bar

RNA Velocity: a mathematical model to predict cellular differentiations

In genetics and genomics, more and more researchers get interested in modelling continuous cellular differentiations thanks to “gene activities” (synthesis of RNA). In this talk, we present a recent mathematical model, named RNA Velocity, which aims to compute vectors indicating the direction of developments inside large samples of cells. We also describe some perspectives for this tool in the detection of genes responsible of specific cellular specializations, which constitutes the core of our research project in GIGA (ULiège) for the next years

Diametral dimension and property Omega Bar for spaces Snu

Spaces Snu are metrizable sequence spaces defined by Jaffard in the context of multifractal analysis and signal treatment. From a functional analysis point of view, the study of these spaces points out some topological properties, such as the facts they are locally pseudoconvex in general and locally p-convex in certain cases, Schwartz, and non-nuclear. In this talk, we focus on two topological invariants, namely the diametral dimension (Bessaga, Mityagin, Pelczynski, Rolewicz) and the property "Omega Bar" (Vogt, Wagner). Firstly, we revisit a result of Aubry and Bastin giving the diametral dimension of locally p-convex spaces Snu and extend it to some non-locally p-convex spaces Snu. Secondly, we explain how these developments can be used to prove that a subclass of spaces Snu (among which the locally p-convex ones) verifes the condition Omega Bar

Invariant subspace problem

La présentation débute par la définition du problème du sous-espace invariant. Après quelques cas simples, elle aborde l'historique de ce problème et donne plusieurs résultats déjà connus

An open question about diametral dimensions

The diametral dimension is a topological invariant which characterizes Schwartz and nuclear spaces. However, there exists another diametral dimension which was conjectured by Bessaga, Mityagin, Pełczynski, and Rolewicz to be equal to the first one in Fréchet spaces. In this talk, we describe some conditions which assure the equality of the two diametral dimensions in metrizable locally convex spaces. Besides, we explain why such an equality is generally impossible in non-metrizable spaces