15 research outputs found

    Determining epigenetic memory in kidney proximal tubule cell derived induced pluripotent stem cells using a quadruple transgenic reprogrammable mouse

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    The majority of nucleated somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs). The process of reprogramming involves epigenetic remodelling to turn on pluripotency-associated genes and turn off lineage-specific genes. Some evidence shows that iPSCs retain epigenetic marks of their cell of origin and this epigenetic memory influences their differentiation potential, with a preference towards their cell of origin. Here, we reprogrammed proximal tubule cells (PTC) and tail tip fibroblasts (TTF), from a reprogrammable mouse to iPSCs and differentiated the iPSCs to renal progenitors to understand if epigenetic memory plays a role in renal differentiation. This model allowed us to eliminate experimental variability due to donor genetic differences and transfection of the reprogramming factors such as copy number and integration site. In this study we demonstrated that early passage PTC iPSCs and TTF iPSCs expressed low levels of renal progenitor genes and high levels of pluripotency-associated genes, and the transcriptional levels of these genes were not significantly different between PTC iPSCs and TTF iPSCs. We used ChIP-seq of H3K4me3, H3K27me3, H3K36me3 and global DNA methylation profiles of PTC iPSCs and TTF iPSCs to demonstrate that global epigenetic marks were not different between the cells from the two different sets of tissue samples. There were also no epigenetic differences observed when kidney developmental genes and pluripotency-associated genes were closely examined. We did observe that during differentiation to renal progenitor cells the PTC iPSC-derived renal cells expressed higher levels of three renal progenitor genes compared to progenitors derived from TTF iPSCs but the underlying DNA methylation and histone methylation patterns did not suggest an epigenetic memory basis for this

    Signal requirement for cortical potential of transplantable human neuroepithelial stem cells.

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    The cerebral cortex develops from dorsal forebrain neuroepithelial progenitor cells. Following the initial expansion of the progenitor cell pool, these cells generate neurons of all the cortical layers and then astrocytes and oligodendrocytes. Yet, the regulatory pathways that control the expansion and maintenance of the progenitor cell pool are currently unknown. Here we define six basic pathway components that regulate proliferation of cortically specified human neuroepithelial stem cells (cNESCs) in vitro without the loss of cerebral cortex developmental potential. We show that activation of FGF and inhibition of BMP and ACTIVIN A signalling are required for long-term cNESC proliferation. We also demonstrate that cNESCs preserve dorsal telencephalon-specific potential when GSK3, AKT and nuclear CATENIN-ÎČ1 activity are low. Remarkably, regulation of these six pathway components supports the clonal expansion of cNESCs. Moreover, cNESCs differentiate into lower- and upper-layer cortical neurons in vitro and in vivo. The identification of mechanisms that drive the neuroepithelial stem cell self-renewal and differentiation and preserve this potential in vitro is key to developing regenerative and cell-based therapeutic approaches to treat neurological conditions

    E-révolutions et révolutions

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    Ce que l'on a pris l’habitude d’appeler les « Printemps arabes » draine son lot de mythes et de fantasmes, et nombre de textes se contentent d’apprĂ©hender la surface des mouvements avec un regard mĂȘlant fascination et exaltation pour les rĂ©seaux sociaux. Or, les reflets numĂ©riques de l’expression contestataire ne suffisent pas Ă  expliquer le phĂ©nomĂšne. Il faut prĂ©fĂ©rer la connaissance des causes profondes animant les agents et les sujets. À cette fin, trois champs sont investis : les trajectoires de mobilisation, les structurations socio-Ă©conomiques sous-jacentes et la nature des revendications. À la croisĂ©e du droit et de la science politique, E-rĂ©volutions et rĂ©volutions remet en cause les clichĂ©s et propose une nouvelle lecture des rĂ©voltes qui ont secouĂ© le monde arabo-musulman en 2011 et 2012. Il analyse les jeux de miroirs dĂ©formants vĂ©hiculĂ©s par les technologies numĂ©riques, les mĂ©canismes de rĂ©gulation Ă©mergents et l’apparition d’un nouvel acteur : le contestataire-participant.The so-called “Arab Springs” give rise to a number of myths and phantasms, and a lot of texts only consider the surface of movements, with both fascination and exaltation about social networks. But the digital expression of contestation is not sufficient to explain the phenomenon. It is preferable to consider deep reasons moving agents and subjects, within three fields of investigation: mobilization trajectories, underlying socio-Ă©conomic structurations, and the nature of the revendications. At the crossroads of law and political science, E-rĂ©volutions et rĂ©volutions shatters clichĂ©s and gives a new vision of revolts in Arabo-Muslim world in 2011 and 2012

    GammapyVersion 0.19

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    Gammapy is a community-developed, open-source Python package for gamma-ray astronomy built on Numpy, Scipy and Astropy. It is the core library for the CTA science tools and can also be used to analyse data from existing imaging atmospheric Cherenkov telescopes (IACTs), such as H.E.S.S., MAGIC and VERITAS. It also provides some support for Fermi-LAT and HAWC data analysis
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