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Epithelial cell death is widespread during development and tissue homeostasis. While the core pathway of apoptosis is well known, we lack predictive power to understand when and where a specific cell will die in […]

Epigenetic mechanisms are considered to be central to the development of multicellular organisms made of different cell types, all having identical genomes. Similarly, they may explain how genetically identical organisms are capable of adapting […]

Désolé, cet article est seulement disponible en EN.

Désolé, cet article est seulement disponible en EN.

Disorders/differences in Sex Development (DSD) are defined as congenital conditions with discordant development of chromosomal and gonadal/anatomical sex and cover a wide range of phenotypes that involve the endocrine and reproductive systems. In the […]

Adult muscle satellite (stem) cells are quiescent during homeostasis. We showed that Notch signaling is highest in quiescent muscle satellite cells, and this activity drops dramatically before the first cell division after muscle injury […]

Symmetric and asymmetric divisions also play key roles during growth and regeneration. We showed previously that asymmetric template DNA strand cosegregation takes place in a subpopulation of adult muscle stem cells (7). More recently […]

The brain faces many environmental challenges throughout life. Maternal malnutrition impacts on the development of the fetal brain, and in adulthood infections such as bacterial meningitis can lead to long-term cognitive deficit. But the […]

Cell-cell signaling mediated by Notch receptors regulates a wide range of developmental processes and perturbations of Notch signaling activity underlie various human developmental and adult-onset diseases, including T-cell leukemia and other cancers. Additionally, Notch […]

Asymmetric Cell Division (ACD) is a simple and conserved mechanism to generate cell diversity during embryogenesis and throughout adult life. In this process, a mother cell divides to generate two daughter cells with distinct […]

Ageing is associated with losing normal cellular plasticity (regeneration capacity) while acquiring abnormal cellular dys-plasticity (cancer). Cellular reprogramming is associated with a gain in the potential for differentiation and self-renewal. Could common pathways be […]

Aberrant cellular plasticity (“dys-plasticity”) could occur in vivo, which contributes significantly to disease development, especially in cancer. Recently, we showed p27-/- cells are dysplastic due to the derepression of Sox2, an essential pluripotency gene. […]

A major gap in the field is the lack of appropriate cellular models to study human SD. This is particularly pressing since we are identifying differences between the human and mouse SD systems. We […]

Stem cells are defined by their is their capacity for self-renewal and differentiation. Some adult tissues maintain a reservoir of stem cells, that generally reside within specialized microenvironments, known as stem cell niches, that […]

This type of transgenesis consists in the microinjection of the gene of interest into the pronucleus of fertilized eggs to generate transgenic mice expressing the transgene. The microinjected transgenes, which integrated randomly into the […]

Despite the detailed characterisation of the molecular players of apoptosis, its orchestration and fine regulation in multicellular contexts is not well understood. While apoptosis is often considered as a simple binary process, there are nowadays many evidences showing […]

Cell fate decisions requiring appropriate transcriptional regulation key genes. SRY is pivotal in mammalian SD but how the expression of SRY is regulated in mammals is unknown. We identified a family from central India […]

Embryonic development requires that the behaviour of thousands of cells be finely orchestrated in concert with signalling pathways. While much work has focused on the genetic and transcriptional control of morphogenesis, how cell dynamics […]

The maintenance of genome integrity plays a key role in the regeneration potential of stem cells, which are responsible for the homeostasis and regeneration of the tissue throughout life. DNA double strand breaks (DSBs) […]

Epithelia form sheets of interconnected cells that are polarized along an apical-basal axis and perform selective exchange and barrier functions. Epithelia are dynamic structures that undergo remodeling associated with cell shape changes and neighbor […]

Genetic and Epigenetic Regulation of Stem Cell Fate The objective of this research programme is to identify mouse stem cell properties and understand how they regulate cell fate choice in different contexts by modulating […]

Neural stem cells (NSCs) are self-renewing and multipotent progenitors generating neurons and glia in the adult vertebrate brain. The success of NSC maintenance and mobilization varies widely among species, brain territories, pathological conditions and […]

Limb defects, which are amongst the most frequent congenital malformations in humans, are the result of deviation in normal developmental program deployment affecting limb specification, initiation or patterning. In most cases the mechanisms underlying […]

Macrophages are professional phagocytic cells that orchestrate homeostatic and innate immune functions, via the scavenging of cells, debris, and pathogens, and the production of cytokines, both concurring to tissue homeostasis and repair. This project […]

The goal of this project is to deliver a new theoretical framework to understand how transcription factors (TFs) sustain cell identity during developmental processes. Recognised as key drivers of cell fate acquisition, TFs are […]

Despite our deep knowledge of the pathways regulating cell proliferation, growth and survival, we still do not understand how single cells can match their behavior to properties of the entire tissue (including its size and shape).  Mechanical […]

We are interested in understanding how variation in morphogentetic processes we have uncovered in chick and mouse can result in variation in shapes and patterns observed in nature. For example we are interested in […]

For many developmental processes, the list of the required elements (genes/molecules) is known but the resulting dynamics is often poorly understood. Thus, in most developmental patterning processes, the relative importance of external positional cues […]

The nucleases (ZFN pairs, TALE pairs, Cas9/CRISPR system) are microinjected, mainly in its mRNA form, into the pronucleus and/or the cytoplasm of one-cell mouse/rat embryos in order to get the desired targeted modification. These […]

The paired/ homeodomain genes Pax3 and Pax7, act primarily in somites to regulate stem/progenitor cells in the body whereas Tbx1 and Pitx2 play critical roles in cranial mesoderm derived muscles in the head. Subsequently, […]

The microinjection of the CRISPR/Cas9 system in one-cell embryos is actually revolutionizing the in vivo genome-engineering field because of its big efficiency for KO/ KI (when a donor DNA matrix co-injected with the CRISPR/CAS9 […]

During embryonic development, both biochemical and mechanical cues establish the cell differentiation patterns that shape tissues and organs. While the role of signaling molecules has been widely studied, how mechanical forces affect progenitor cell […]

During tissuegenesis, muscle stem cells generate phenotypically and functionally distinct embryonic and foetal myoblasts (1, 2). We used genetically modified mice and constitutively expressed the intracellular domain of Notch1 receptor (NICD) to block the […]

The goal of this project is to develop a new organ-on-chip microfluidic device based on the actuation of thin hydrogel layers. Indeed, hydrogels possess interesting properties, compared to the commonly used perforated PDMS membranes. […]

The goals of this project are to build an external bioartificial liver, a liver-on-chip as well as a bioengineered liver. In the present project, bioconstruction of the liver will be performed by the assembly […]

The intestine, and in particular the colon, comprising a mucus blanket, an epithelial monolayer and the lamina propria rich in immune cells, is constantly subjected to shear stress (flow) and peristaltic motion (stretching), both […]

The preservation of pluripotency throughout cell division – self-renewal -, is strictly dependent on the highly efficient action of the pluripotency gene regulatory network. However, how TFs cope with replication and mitosis, two major […]

Morphogenesis, that is the acquisition of a shape, is essential for organ function. The heart is an asymmetric organ, in which the left and right sides are fully separated to drive the double blood […]

Lentiviral transgenesis is a special type of classical/additive transgenesis. The transgene, inserted in a lentiviral construct, is microinjected directly under the zona pellucida of one-cell embryos. Then viruses are able to enter directly the […]

Our data on the role of nuclear receptors in human ovarian development and the repression of WNT signaling during mammalian testis formation suggests the main function of pro-testis genes may be to antagonize pro-ovary […]

The mechanisms governing ageing, which is a multifactorial process, have not been resolved and constitute a fundamental open question in cell and organismal biology. Ageing is dramatically accelerated in some rare genetic disorders. Dissecting […]

Growth of the heart is required to adapt to the increasing hemodynamic load of the developing organism. Physiologically, heart growth is mainly driven by the proliferation of myocardial cells in utero and by cell […]

The use of new technological approaches including microfluidics and organ-on-chip strategies has permitted the design of advanced in vitro assays to address a variety of questions including in the study of human infections.  These […]

Welcome to the club! Welcome to Microfluidics@Pasteur! Our goal is to serve as the major entry point to all the scientists on the campus (beginners and experts) interested in undertaking projects where microfluidics is involved. Our […]

The easy availability of modified ES cells obtained from KOMP and EUCOMM high-throughput gene-targeting mutagenesis programs (mainly JM8.N4, JM8 A3.N1 ES cell lines) has considerably increased the requests for these direct microinjections in the […]

The behaviour of muscle stem cells during sepsis Sepsis is an uncontrolled immune reaction that occurs in approximately 2% of all hospitalizations in developed countries. Patients die in 30% of the cases (up to […]

What’s best to study humans and their infectious deseases than Human emulation system ? It’s now possible at Pasteur to develop real Organs-on-chips with cells from different sources, patient derived or cell line. At […]

Our objective is to generate inner ear organoids that can recapitulate in vitro the initial steps of the cochlear epithelium formation. In particular, we aim at generating these organoids in a micro-environment that allows […]

We have an increasing experience in modification on rat genome using lentiviral vectors and Zinc Finger Nucleases (ZFNs). Rat models are more convenient for surgery, due to their medium size, and constitute a robust […]

We use a number of genetically modified mice to interrogate specific functions of stem/progenitor cells during the establishment of muscle and its reconstitution after injury. These include mutants for Myf5, Pax7, Myod, Tbx1, RBPJk, […]

A gene targeting vector is transfected into the desired mouse ES cells to modify an endogenous gene by homologous recombination. The mutant ES cells thus obtained are subsequently microinjected into mouse blastocysts for the […]

The study of ES cells has not escaped the recent explosion of regulatory lncRNA biology: from the thousands of lncRNAs that have been identified across the mouse genome a large subset is expressed in […]

Self-renewing ES cells display dramatic cell-to-cell variability in the expression level of key transcription factors such as Nanog. Whereas Nanog-positive cells self-renew efficiently, Nanog-negative cells are prone to differentiate. Although these two populations can dynamically inter-convert, very […]

The identification of variants in DHX37 as a cause of 46,XY DSD opens up the possibility that some forms of human sex-reversal are ribosomopathies. Pathogenic variants associated with a lack of testis-determination or, the […]

Vertebrate adult neural stem cells (NSCs) are generally quiescent, and the frequency of their cell cycle re-entry (“activation”) conditions their lifespan. Little is known of the molecular pathways controlling the NSC quiescence/activation balance. We […]