Комплексные омики обнаруживают связанные с болезнями радиальные глиаподобные клетки с эпигенетически регулируемой интерферонной реакцией при множественном склерозе.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Park Bongsoo, Nicaise Alexandra M, Tsitsipatis Dimitrios, Pirvan Liviu, Zucha Daniel, Munteanu Andi, Prasad Pranathi, De Novales Miguel Larraz Lopez, Bulgaru Cristian, Kollyfas Rafael, Whitten Julia, Willis Cory M, Culig Luka, Llewellyn Joseph, Ionescu Rosana-Bristena, Mekdad Magdy, Simões-Abade Madalena B C, Krzak Grzegorz, Fan Jinshui, De Supriyo, Ellis Matthew O, Cubero Marta Suarez, Spathopoulou Angeliki, Peruzzotti-Jametti Luca, Leonardi Tommaso, Balmus Gabriel, Edenhofer Frank, Gorospe Myriam, Valihrach Lukas, Mohorianu Irina, Pluchino Stefano, Beerman Isabel
Аннотация
Оригинал публикации
Integrated omics reveals disease-associated radial glia-like cells with epigenetically dysregulated interferon response in multiple sclerosis.
Progressive multiple sclerosis (PMS) involves a persistent, maladaptive inflammatory process with numerous cellular drivers. We generated induced neural stem cells (iNSCs) from patient fibroblasts through a direct reprogramming protocol that preserved their epigenome, which revealed a PMS-specific hypomethylation of lipid metabolism and interferon (IFN) signaling genes. Single-cell multi-omics uncovered a novel, disease-associated radial glia-like cell (DARG) subpopulation in PMS cell lines exhibiting senescence and potent IFN responsiveness driven by specific transcription factors. Functionally, PMS iNSCs induced paracrine senescence and inflammation onto control cells, which was inhibited upon senolytic treatment. We identified in PMS brains a distinct population of senescent, IFN-responsive DARGs that developmentally aligned with the trajectories of iNSCs in vitro and spatially associated with inflammatory glia in chronically active lesions. DARGs may sustain smoldering inflammation, unveiling a previously unrecognized cellular axis that could underpin mechanisms in neurodegeneration. This discovery offers novel insights into disease mechanisms and highlights potential therapeutic targets.