PT - JOURNAL ARTICLE AU - Sibiao Yue AU - Xiaobin Zheng AU - Yixian Zheng TI - Cell type-specific role of lamin-B1 and its inflammation-driven reduction in organ building and aging AID - 10.1101/448837 DP - 2018 Jan 01 TA - bioRxiv PG - 448837 4099 - http://biorxiv.org/content/early/2018/10/20/448837.short 4100 - http://biorxiv.org/content/early/2018/10/20/448837.full AB - Cellular architectural proteins often participate in organ development and maintenance. Although functional decay of some of these proteins during aging is known, the cell-type specific developmental role and the cause and consequence of their subsequent decay remain to be established especially in mammals. By studying lamins, the nuclear structural proteins, we demonstrate that lamin-B1 functions specifically in the thymic epithelial cells (TECs) for proper thymus organogenesis. An upregulation of proinflammatory cytokines in the intra-thymic myeloid immune cells during aging accompanies a gradual reduction of adult TEC lamins-B1. These cytokines cause adult TEC senescence and lamin-B1 reduction. We identify 17 adult TEC subsets and show that TEC lamin-B1 maintains the composition of these TECs. Lamin-B1 supports the expression of TEC genes needed for maintaining adult thymic architecture and function. Thus, structural proteins involved in organ building and maintenance can undergo inflammation-driven decay which can in turn contribute to age-associated organ degeneration.