Nuclear pore complexes (NPCs) are necessary for stem cell maintenance, cell fate determination, and the aging process. The specific contribution of NPCs to the physiology of muscle stem cells (satellite cells, SCs) is largely unknown. Here we show that NPCs are essential for the correct function of SCs and that they suffer an age-dependent deterioration. The downregulation of the nucleoporin
TPR in proliferating SCs induces senescence as well as chromatin reorganization, increased incorporation of repressive epigenetic marks and DNA damage. Furthermore, it causes activation of the Hippo and the cGAS-STING pathways, thus mimicking the aberrant Hippo activation naturally observed with aging in geriatric SCs. cGAS-STING activation in TPR-depleted SCs is dependent on YAP activation, indicative of the interplay between these two signaling pathways. Our results identify NPCs as critical regulators of SC fitness, senescence development in muscle, and the age-dependent decline of SCs.
(Universitat Pompeu Fabra, 2023-05-26T14:40:56Z) Cuenca Cortés, Alejandro; Muñoz Cánoves, Pura; Universitat Pompeu Fabra. Departament de Medicina i Ciències de la Vida
