ENA0000GenomicsHartwell Center, St Jude Childrens Research Hospitalhttps://www.ebi.ac.uk/ena/browser/view/PRJNA322694Mus musculusIL-7 r and Stat5 signaling drives early B lymphopoiesis, but it remains poorly understood how Stat5-dependent and independent pathways contribute to this process. We report the discrete effects of PI3K and mTOR signaling on Stat5 signaling and B cell development. PI3K was not engaged by IL-7 in pro-B cells but was actively suppressed by PTEN to ensure proper IL-7 r expression, Stat5 signaling and pro-B cell survival. Further, IL-7-mediated mTORC1 activation, which was uncoupled from PI3K signaling, orchestrated a unique program in early B cell development in a Stat5-independent but Myc-dependent manner. mTORC1 was also required for immunoglobulin heavy chain rearrangement and Myc-driven lymphomagenesis. Finally, mTORC2 was not essential for early B cell development but contributed to peripheral B cell maturation. Altogether, genetic dissection of PI3K, mTORC1, and mTORC2 reveals the distinct effects of these seemingly related pathways on B cell development and the intricate interplay between PI3K, mTOR and IL-7 r-Stat5 signaling. Overall design: We used microarrays to explore the gene expression profiles differentially expressed in untreated and IL-7 treated B220+CD43+IgM- pro-B cells from Cre^(ER)/Rptor^(fl/+) and Cre^(ER)/Rptor^(fl/fl) mice 7 days after tamoxifen treatment.ENAhlb368, biological signaling, 2610315D21Rik, dP60, CG5373, ATVPS34, Vps34, GLM2, PI3K92E, FKBP12-rapamycin complex-associated protein, CG5092, Il-7, DPTEN, interleukin-7 receptor ligand, PI3K, Pi3K_59F, Dp110, BcDNA:LD15217, l(2)k03905, type I phosphatidylinositol kinase activity, VPS34, 11621, l(2)k17004, phosphatidylinositol 3-kinase, DmTOR, PI-3 kinase, p110-alpha, MHAM, PIK3, PHOSPHATIDYLINOSITOL 3-KINASE, Pi3Kp60, dVps34/PI3K59F, DmelCG2699, F8A5.4, p60, PI3K-dp110, AI463227, IL-7, dPI3K, PHOSPATIDYLINOSITOL 3-KINASE, TEP1, anon-92Ed, phosphatidylinositol 3-kinase activity, RAFT1, TOR, Mammalian target of rapamycin, Dp110/PI3K, PI3K-68D/E, DmelCG8274, class I, Dp60, B-lymphocyte differentiation, Bx34, Pi3K92D, CG4141, PI3K_59F, catalyst activity, Pi3k, PI3-kinase activity, flat, tor, PI3'K, Tpr, TPR, PI[[3]]K, Pi3Kp110, DmelCG5671, PI3Kgamma, dtor, P110BETA, MCAP, PI3K-68D, p55alpha, PI3K21B, signaling process, B lymphocyte differentiation, PI3K 68D, B430203M17Rik, Pi3K, PI3k, IL7, MCM, Frap1, MCMTC, CT24817, ATP - 1-phosphatidyl-1D-myo-inositol 3-phosphotransferase activity, dTOR, dTor, FK506-binding protein 12-rapamycin complex-associated protein 1, single organism signaling, Cpk, signalling., dP110, Mechanistic target of rapamycin, dVps34, PI3K68D, Stat5, PTEN, AA414921, P110DELTA, p120, class II, PtdIns-3-kinase activity, rea, type III phosphoinositide 3-kinase activity, B-cell differentiation, p50alpha, p110, dPten, Vps34p, FRAP1, FRAP2, mTOR, pten, FRAP/TOR, DmelCG5092, CG2699, PI(3)K, vacuolar protein sorting 34, DmelCG5373, cpk, dPIK, 1-phosphatidylinositol 3-kinase activity, PI3K-92E/Dp110, dpten, PIK3C1, 2.7.11.1, ATP:1-phosphatidyl-1D-myo-inositol 3-phosphotransferase activity, C530050K14, PTEN3, CWS5, vps34, PTEN1, CWS1, type-1 PI3K, dp110, dPTEN, PI3CG, RAPT1, PI-3-K, CG11621, PI3K-59F, A630026I06Rik, Mmac, 10q23del, CG5671, p85alpha, PI3K-Dp110, MMAC1, Rapamycin and FKBP12 target 1, class III, CT24745, Rapamycin target protein 1, AI327068, DmelCG11621, PI3K 68_D, A130070J02Rik, STAT5, PTENa, p110gamma, FRAP, DmelCG4141, F8A5_4, APDS, DEC, p110D, CLOVE, CT16317, signalling process, DmVps34, IMD14, stat5, B cell development, PI3K_68D, CG8274, 5092, PI3KBETA, PI3K-92D, MGF, MTOR, AA959963, regulation, Dmp110, p120-PI3K, BZS, droPIK57, 2310035O07Rikmouse, mouse <Mus musculus>, house mouse.0.00.00.00.00.00falseMus musculusB cell development requires discrete regulation by PTEN-PI3K and mTOR pathways and the intricate interplay with IL-7 r-Stat5 signaling2022-05-122018-03-01PRJNA322694GSE818442939963310090