Although a large portion of the human genome is actively transcribed, only a fraction of these RNAs are protein-coding genes. It is now well appreciated that these non-coding transcripts are not only highly diverse in size and structure, but are functional and can exert effects on a vast number of cellular processes. Long intergenic non-coding RNAs (lincRNA) have recently been shown to be key regulators of gene expression during development and oncogenesis. While the growth factors, signaling pathways, and microRNAs that govern lymphoid development and function have been extensively studied, the contribution of these long non-coding RNAs remains poorly characterized. To address this, we performed a genome-wide analysis of lincRNA expression throughout lymphoid and T-lineage development. Bone marrow lymphoid primed multipotent progenitors, DN1-4 and DP thymocytes, as well as mature naïve CD4+ T cells and differentiated helper T cells were sorted and subjected to RNAseq analysis; multiple unique lincRNAs were identified at each stage of development. Transgenic knockout mice were then generated for candidate lincRNAs and analyzed to characterize their function. Through this approach we have identified lincRNAs that regulate both early T lineage and lymphoid commitment as well as mature T cell differentiation and function. These findings offer novel insight into the regulation of lymphoid development and function and expand our understanding of the role non-coding transcripts play in hematopoiesis.
Citation Format: Will Bailis, Christian Harman, Jorge Henao-Mejia, Adam Williams, Loyall Goff, John Rinn, Richard Flavell. Identification and characterization of long intergenic non-coding RNAs (lincRNAs) governing T cell development and function [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A071.
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