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ItemTCF-1 limits the formation of Tc17 cells via repression of the MAF-ROR gamma t axisMielke, LA ; Liao, Y ; Clemens, EB ; Firth, MA ; Duckworth, B ; Huang, Q ; Almeida, FF ; Chopin, M ; Koay, H-F ; Bell, CA ; Hediyeh-Zadeh, S ; Park, SL ; Raghu, D ; Choi, J ; Putoczki, TL ; Hodgkin, PD ; Franks, AE ; Mackay, LK ; Godfrey, D ; Davis, MJ ; Xue, H-H ; Bryant, VL ; Kedzierska, K ; Shi, W ; Belz, GT (ROCKEFELLER UNIV PRESS, 2019-07-01)Interleukin (IL)-17-producing CD8+ T (Tc17) cells have emerged as key players in host-microbiota interactions, infection, and cancer. The factors that drive their development, in contrast to interferon (IFN)-γ-producing effector CD8+ T cells, are not clear. Here we demonstrate that the transcription factor TCF-1 (Tcf7) regulates CD8+ T cell fate decisions in double-positive (DP) thymocytes through the sequential suppression of MAF and RORγt, in parallel with TCF-1-driven modulation of chromatin state. Ablation of TCF-1 resulted in enhanced Tc17 cell development and exposed a gene set signature to drive tissue repair and lipid metabolism, which was distinct from other CD8+ T cell subsets. IL-17-producing CD8+ T cells isolated from healthy humans were also distinct from CD8+IL-17- T cells and enriched in pathways driven by MAF and RORγt Overall, our study reveals how TCF-1 exerts central control of T cell differentiation in the thymus by normally repressing Tc17 differentiation and promoting an effector fate outcome.
ItemHaemopedia RNA-seq: a database of gene expression during haematopoiesis in mice and humansChoi, J ; Baldwin, TM ; Wong, M ; Bolden, JE ; Fairfax, KA ; Lucas, EC ; Cole, R ; Biben, C ; Morgan, C ; Ramsay, KA ; Ng, AP ; Kauppi, M ; Corcoran, LM ; Shi, W ; Wilson, N ; Wilson, MJ ; Alexander, WS ; Hilton, DJ ; de Graaf, CA (OXFORD UNIV PRESS, 2019-01-08)During haematopoiesis, haematopoietic stem cells differentiate into restricted potential progenitors before maturing into the many lineages required for oxygen transport, wound healing and immune response. We have updated Haemopedia, a database of gene-expression profiles from a broad spectrum of haematopoietic cells, to include RNA-seq gene-expression data from both mice and humans. The Haemopedia RNA-seq data set covers a wide range of lineages and progenitors, with 57 mouse blood cell types (flow sorted populations from healthy mice) and 12 human blood cell types. This data set has been made accessible for exploration and analysis, to researchers and clinicians with limited bioinformatics experience, on our online portal Haemosphere: https://www.haemosphere.org. Haemosphere also includes nine other publicly available high-quality data sets relevant to haematopoiesis. We have added the ability to compare gene expression across data sets and species by curating data sets with shared lineage designations or to view expression gene vs gene, with all plots available for download by the user.