In vivo imaging of mammary epithelial cell dynamics in response to lineage-biased Wnt/β-catenin activation

International audienceHighlights d Lineage-biased b-catenin activation in mammary cells leads to hyperplastic lesions d Intravital imaging reveals mammary cell dynamics induced by b-catenin activation d Constitutive Wnt signaling induces squamous transdifferentiation of mammary cell

Notch Lineages and Activity in Intestinal Stem Cells Determined by a New Set of Knock-In Mice

The conserved role of Notch signaling in controlling intestinal cell fate specification and homeostasis has been extensively studied. Nevertheless, the precise identity of the cells in which Notch signaling is active and the role of different Notch receptor paralogues in the intestine remain ambiguous, due to the lack of reliable tools to investigate Notch expression and function in vivo. We generated a new series of transgenic mice that allowed us, by lineage analysis, to formally prove that Notch1 and Notch2 are specifically expressed in crypt stem cells. In addition, a novel Notch reporter mouse, Hes1-EmGFPSAT, demonstrated exclusive Notch activity in crypt stem cells and absorptive progenitors. This roster of knock-in and reporter mice represents a valuable resource to functionally explore the Notch pathway in vivo in virtually all tissues

Clonal analysis of Notch1-expressing cells reveals the existence of unipotent stem cells that retain long-term plasticity in the embryonic mammary gland.

Recent lineage tracing studies have revealed that mammary gland homeostasis relies on unipotent stem cells. However, whether and when lineage restriction occurs during embryonic mammary development, and which signals orchestrate cell fate specification, remain unknown. Using a combination of in vivo clonal analysis with whole mount immunofluorescence and mathematical modelling of clonal dynamics, we found that embryonic multipotent mammary cells become lineage-restricted surprisingly early in development, with evidence for unipotency as early as E12.5 and no statistically discernable bipotency after E15.5. To gain insights into the mechanisms governing the switch from multipotency to unipotency, we used gain-of-function Notch1 mice and demonstrated that Notch activation cell autonomously dictates luminal cell fate specification to both embryonic and basally committed mammary cells. These functional studies have important implications for understanding the signals underlying cell plasticity and serve to clarify how reactivation of embryonic programs in adult cells can lead to cancer.Wellcome Trus

La sclérose en plaques (immunologie, traitements et perspectives d'avenir)

La sclérose en plaques (SEP) est une maladie auto-immune chronique du système nerveux central. La maladie se caractérise par la destruction de la gaine de myéline perturbant la conduction de l influx nerveux. Les symptômes sont variés : troubles sensitifs, visuels, moteurs, fatigue, douleurs La maladie est caractérisée par une succession de phases de poussées et de rémissions. La prise en charge de la SEP est basée sur le traitement des poussées, le traitement de fond pour réduire la fréquence des rechutes et la progression du handicap ; et le traitement symptomatique pour atténuer la gêne quotidienne. La recherche progresse et vise à mieux comprendre les modalités qui pourraient être mises en oeuvre pour protéger le système nerveux au cours de cette maladie. De nombreuses molécules sont en cours d essais cliniques dans le but d améliorer la prise en charge globale de la pathologie.LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

Notch3 marks clonogenic mammary luminal progenitor cells in vivo

The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive “triple negative” human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2SAT transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells.</jats:p

Notch3 marks clonogenic mammary luminal progenitor cells in vivo

The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive “triple negative” human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2(SAT) transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells

Alternatives au glyphosate en grandes cultures. Evaluation économique: Evaluation économique

Travail réalisé à la demande du Premier Ministre et des Ministres en charge de l'Agriculture et la Transition Ecologique et Solidaire, dans le cadre du plan de sortie du glyphosate.Alternatives au glyphosate en grandes cultures . Evaluation économiqu

Alternatives au glyphosate en grandes cultures. Evaluation économique. Résumé exécutif

Alternatives au glyphosate en grandes cultures. Evaluation économique. Résumé exécuti