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Kiskinis, Evangelos

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Kiskinis

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Evangelos

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Kiskinis, Evangelos

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2012 - 20142

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Author's Publications: search.filters.isAuthorOfPublication.9fcb7623-3b21-41f2-af6a-998309297bf5

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    Erosion of Dosage Compensation Impacts Human iPSC Disease Modeling
    (Elsevier BV, 2012) Mekhoubad, Shila; Bock, Christoph; de Boer, A. Sophie; Kiskinis, Evangelos; Meissner, Alexander; Eggan, Kevin
    Although distinct human induced pluripotent stem cell (hiPSC) lines can display considerable epigenetic variation, it has been unclear whether such variability impacts their utility for disease modeling. Here, we show that although low-passage female hiPSCs retain the inactive X chromosome of the somatic cell they are derived from, over time in culture they undergo an “erosion” of X chromosome inactivation (XCI). This erosion of XCI is characterized by loss of XIST expression and foci of H3-K27-trimethylation, as well as transcriptional derepression of genes on the inactive X that cannot be reversed by either differentiation or further reprogramming. We specifically demonstrate that erosion of XCI has a significant impact on the use of female hiPSCs for modeling Lesch-Nyhan syndrome. However, our finding that most genes subject to XCI are derepressed by this erosion of XCI suggests that it should be a significant consideration when selecting hiPSC lines for modeling any disease.
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    Pathways Disrupted in Human ALS Motor Neurons Identified through Genetic Correction of Mutant SOD1
    (Elsevier BV, 2014) Kiskinis, Evangelos; Sandoe, Jackson L; Williams, Lauren; Boulting, Gabriella; Moccia, Robert; Wainger, Brian; Han, Steve Sang-woo; Peng, Theodore; Thams, Sebastian; Mikkilineni, Shravani; Mellin, Cassidy; Merkle, Florian; Davis-Dusenbery, Brandi N; Ziller, Michael; Oakley, Derek; Ichida, Justin; Di Costanzo, Stefania; Atwater, Nick; Maeder, M; Goodwin, Marcus; Nemesh, James; Handsaker, Robert; Paull, Daniel; Noggle, Scott; McCarroll, Steven; Joung, Keith; Woolf, Carl; Brown, Robert H; Eggan, Kevin
    Direct electrical recording and stimulation of neural activity using micro-fabricated silicon and metal micro-wire probes have contributed extensively to basic neuroscience and therapeutic applications; however, the dimensional and mechanical mismatch of these probes with the brain tissue limits their stability in chronic implants and decreases the neuron–device contact. Here, we demonstrate the realization of a three-dimensional macroporous nanoelectronic brain probe that combines ultra-flexibility and subcellular feature sizes to overcome these limitations. Built-in strains controlling the local geometry of the macroporous devices are designed to optimize the neuron/probe interface and to promote integration with the brain tissue while introducing minimal mechanical perturbation. The ultra-flexible probes were implanted frozen into rodent brains and used to record multiplexed local field potentials and single-unit action potentials from the somatosensory cortex. Significantly, histology analysis revealed filling-in of neural tissue through the macroporous network and attractive neuron–probe interactions, consistent with long-term biocompatibility of the device.