Joyeuseté : polka : piano dans le ton de l'orchestre / Alex. Carteron

Titre uniforme : Carteron, Alexandre (18..-1940). Compositeur. [Joyeuseté. Piano

SISTEMA: A large and standardized collection of transcriptome data sets for human pluripotent stem cell research

International audienceHuman pluripotent stem cells have ushered in an exciting new era for disease modeling, drug discovery, and cell therapy development. Continued progress toward realizing the potential of human pluripotent stem cells will be facilitated by robust data sets and complementary resources that are easily accessed and interrogated by the stem cell community. In this context, we present SISTEMA, a quality-controlled curated gene expression database, built on a valuable catalog of human pluripotent stem cell lines, and their derivatives for which transcriptomic analyses have been generated using a single experimental pipeline. SISTEMA functions as a one-step resource that will assist the stem cell community to easily evaluate the expression level for genes of interest, while comparing them across different hPSC lines, cell types, pathological conditions, or after pharmacological treatments

Clinical Aspects of Sjögren’s

Sjögren's is an autoimmune inflammatory disorder of the exocrine glands, particularly affecting lacrimal and salivary glands, which can adversely affect quality of life (QOL) and carry a high illness and financial burden. Hallmark symptoms are dry mouth and eye, often in conjunction with profound fatigue and neurocognitive dysfunction. However, dry mouth and/or dry eye may not be present at disease initiation, which contributes to the diagnostic challenge and under recognition despite high prevalence of the disease. Various extraglandular manifestations, such as neuropathy, gastrointestinal dysmotility, arthralgia, and photosensitive skin rashes, may be presenting signs. The sentinel feature of the disease is lymphocytic, predominantly CD4+ T cells and infiltration of target tissue. Sjögren's can be the primary condition (primary Sjögren's) or co-occur with another autoimmune disease (secondary Sjögren's). Primary Sjögren's is more frequent in women than men, but it may be underrecognized in men and children. Early, accurate diagnosis of Sjögren's can help prevent or ensure adequate treatment of the many complications associated with the disease. With a proactive and multidisciplinary treatment plan, the QOL of Sjögren's patients can be significantly improved and the burden of illness reduced

CRISPR gene editing in pluripotent stem cells reveals the function of MBNL proteins during human in vitro myogenesis

International audienceAlternative splicing has emerged as a fundamental mechanism for the spatiotemporal control of development. A better understanding of how this mechanism is regulated has the potential not only to elucidate fundamental biological principles, but also to decipher pathological mechanisms implicated in diseases where normal splicing networks are misregulated. Here, we took advantage of human pluripotent stem cells to decipher during human myogenesis the role of muscleblind-like (MBNL) proteins, a family of tissue-specific splicing regulators whose loss of function is associated with myotonic dystrophy type 1 (DM1), an inherited neuromuscular disease. Thanks to the CRISPR/Cas9 technology, we generated human-induced pluripotent stem cells (hiPSCs) depleted in MBNL proteins and evaluated the consequences of their losses on the generation of skeletal muscle cells. Our results suggested that MBNL proteins are required for the late myogenic maturation. In addition, loss of MBNL1 and MBNL2 recapitulated the main features of DM1 observed in hiPSC-derived skeletal muscle cells. Comparative transcriptomic analyses also revealed the muscle-related processes regulated by these proteins that are commonly misregulated in DM1. Together, our study reveals the temporal requirement of MBNL proteins in human myogenesis and should facilitate the identification of new therapeutic strategies capable to cope with the loss of function of these MBNL proteins

CRISPR gene editing in pluripotent stem cells reveals the function of MBNL proteins during human in vitro myogenesis

International audienceAlternative splicing has emerged as a fundamental mechanism for the spatiotemporal control of development. A better understanding of how this mechanism is regulated has the potential not only to elucidate fundamental biological principles, but also to decipher pathological mechanisms implicated in diseases where normal splicing networks are misregulated. Here, we took advantage of human pluripotent stem cells to decipher during human myogenesis the role of muscleblind-like (MBNL) proteins, a family of tissue-specific splicing regulators whose loss of function is associated with myotonic dystrophy type 1 (DM1), an inherited neuromuscular disease. Thanks to the CRISPR/Cas9 technology, we generated human-induced pluripotent stem cells (hiPSCs) depleted in MBNL proteins and evaluated the consequences of their losses on the generation of skeletal muscle cells. Our results suggested that MBNL proteins are required for the late myogenic maturation. In addition, loss of MBNL1 and MBNL2 recapitulated the main features of DM1 observed in hiPSC-derived skeletal muscle cells. Comparative transcriptomic analyses also revealed the muscle-related processes regulated by these proteins that are commonly misregulated in DM1. Together, our study reveals the temporal requirement of MBNL proteins in human myogenesis and should facilitate the identification of new therapeutic strategies capable to cope with the loss of function of these MBNL proteins

MBNL dependent-impaired development connectivity within neuromuscular circuits in Myotonic Dystrophy type.

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MBNL dependent-impaired development connectivity within neuromuscular circuits in Myotonic Dystrophy type.

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MBNL‐dependent impaired development within the neuromuscular system in myotonic dystrophy type 1

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