Portail HAL du Collège de France
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Standardized high‐dimensional spectral cytometry protocol and panels for whole blood immune phenotyping in clinical and translational studies
No full textInternational audienceAbstract Flow cytometry is the method of choice for immunophenotyping in the context of clinical, translational, and systems immunology studies. Among the latter, the Milieu Intérieur (MI) project aims at defining the boundaries of a healthy immune response to identify determinants of immune response variation. MI used immunophenotyping of a 1000 healthy donor cohort by flow cytometry as a principal outcome for immune variance at steady state. New generation spectral cytometers now enable high‐dimensional immune cell characterization from small sample volumes. Therefore, for the MI 10‐year follow up study, we have developed two high‐dimensional spectral flow cytometry panels for deep characterization of innate and adaptive whole blood immune cells (35 and 34 fluorescent markers, respectively). We have standardized the protocol for sample handling, staining, acquisition, and data analysis. This approach enables the reproducible quantification of over 182 immune cell phenotypes at a single site. We have applied the protocol to discern minor differences between healthy and patient samples and validated its value for application in immunomonitoring studies. Our protocol is currently used for characterization of the impact of age and environmental factors on peripheral blood immune phenotypes of >400 donors from the initial MI cohort. This article is protected by copyright. All rights reserved
Le conte merveilleux français. Séminaire de Brest et textes inédits: Edition établie et présentée par Nicole Belmont et Josiane Bru
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Creg1 Regulates Erythroid Development via TGF‐β/Smad2‐Klf1 Axis in Zebrafish
No full textInternational audienceUnderstanding the regulation of normal erythroid development will help to develop new potential therapeutic strategies for disorders of the erythroid lineage. Cellular repressor of E1A‐stimulated genes 1 (CREG1) is a glycoprotein that has been implicated in the regulation of tissue homeostasis. However, its role in erythropoiesis remains largely undefined. In this study, it is found that CREG1 expression increases progressively during erythroid differentiation. In zebrafish, creg1 mRNA is preferentially expressed within the intermediate cell mass (ICM)/peripheral blood island (PBI) region where primitive erythropoiesis occurs. Loss of creg1 leads to anemia caused by defective erythroid differentiation and excessive apoptosis of erythroid progenitors. Mechanistically, creg1 deficiency results in reduced activation of TGF‐β/Smad2 signaling pathway. Treatment with an agonist of the Smad2 pathway (IDE2) could significantly restore the defective erythroid development in creg1 −/− mutants. Further, Klf1 , identified as a key target gene downstream of the TGF‐β/Smad2 signaling pathway, is involved in creg1 deficiency‐induced aberrant erythropoiesis. Thus, this study reveals a previously unrecognized role for Creg1 as a critical regulator of erythropoiesis, mediated at least in part by the TGF‐β/Smad2‐Klf1 axis. This finding may contribute to the understanding of normal erythropoiesis and the pathogenesis of erythroid disorders
History of Developing Acute Promyelocytic Leukemia Treatment and Role of Promyelocytic Leukemia Bodies
No full textInternational audienceThe story of acute promyelocytic leukemia (APL) discovery, physiopathology, and treatment is a unique journey, transforming the most aggressive form of leukemia to the most curable. It followed an empirical route fueled by clinical breakthroughs driving major advances in biochemistry and cell biology, including the discovery of PML nuclear bodies (PML NBs) and their central role in APL physiopathology. Beyond APL, PML NBs have emerged as key players in a wide variety of biological functions, including tumor-suppression and SUMO-initiated protein degradation, underscoring their broad importance. The APL story is an example of how clinical observations led to the incremental development of the first targeted leukemia therapy. The understanding of APL pathogenesis and the basis for cure now opens new insights in the treatment of other diseases, especially other acute myeloid leukemias
Apport de la géophysique à la restitution du système hydraulique de Larsa (Iraq du sud) au 2 ème millénaire av J.-C.
No full textInternational audienceIn Larsa (Southern Iraq), a 200 hectares site which dominated Mesopotamia at the beginning of the 2nd millennium BC, the study of the hydraulic system, urban and peri-urban, is in progress. It relies in particular on the geophysical approach, a preferred means of identification and interpretation of buried structures and their mapping. The study of the magnetic signatures of conveyance (canals and pipes), storage (basins) and protection (dykes) works allows, beyond their typological characterization (architectural and architectonic), the functional analysis of a system as vast as it is complex.A Larsa (Iraq du Sud), site de 200 hectares qui domina la Mésopotamie au début du 2e millénaire av. J.-C., l’étude du système hydraulique, urbain et péri-urbain, est en cours. Elle s’appuie notamment sur l’approche géophysique, moyen privilégié d’identification et d’interprétation des structures enfouies et de leur cartographie. L’étude des signatures magnétiques des ouvrages d’adduction (canaux et canalisations), de stockage (bassins) et de protection (digues) permet, au-delà de leur caractérisation typologique (architecturale et architectonique), l’analyse fonctionnelle d’un système aussi vaste que complexe
Dossier : La notion de « polis-religion » à l’épreuve des normes et de l’autorité religieuse
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Brotherly diplomacy: on the Kitan–Mongol model of pseudo-kinship and the origins of the Kitan emperors’ fictive kinship with Chinese rulers
No full textInternational audienceEvidence shows that tenth- and eleventh-century Kitan (Liao) emperors used pseudo-kinship to cement diplomatic relations with foreign powers as well as for internal affairs. Similarities between this practice and twelfth- and thirteenth-century Mongol anda (sworn friendship) were previously highlighted by Wang Guowei but have yet to be the focus of further study. Kitan emperors used pseudo-kinship as a preferred political tool to establish alliances and reinforce their position in both external and domestic policies. A comparison of Kitan and Mongol traditions also shows a high degree of similarity. However, although they share concepts of sworn friendship and common oath rituals, the establishment of pseudo-kinship occurred in different contexts and often for different purposes. This article attempts to show that Kitan rulers successfully continued the pseudo-kinship diplomacy that existed since the Tang between the hegemons of the steppe and the Central Plain. They achieved this by making regular use of pseudo-kinship diplomacy, in addition to seeking ways to make the practice more acceptable to the Chinese court. These adaptations included a progressive estrangement of diplomatic pseudo-kinship from its original form, casting away oath rituals and adopting a new system of kinship terms