Fig. 5: Inhibition of Akt/mTOR pathway ameliorates ASXL1-MT-induced aberrant proliferation of pLT-HSCs. | Nature Communications

Fig. 5: Inhibition of Akt/mTOR pathway ameliorates ASXL1-MT-induced aberrant proliferation of pLT-HSCs.

From: Mutant ASXL1 induces age-related expansion of phenotypic hematopoietic stem cells through activation of Akt/mTOR pathway

Fig. 5: Inhibition of Akt/mTOR pathway ameliorates ASXL1-MT-induced aberrant proliferation of pLT-HSCs.The alternative text for this image may have been generated using AI.

a The experimental design for treatment with an mTOR inhibitor rapamycin in aged mice. Aged Vav-Cre ASXL1-MT KI mice and age-matched control mice were treated with rapamycin intraperitoneally (4 mg/kg/day) every other day for 8 weeks. At the end of administrations, end-point analyses of bone marrow cells were conducted. b, c The frequency of LT-HSCs in bone marrow MNCs (n = 6 (Control-Vehicle), 7 (Control-Rapamycin), 5 (ASXL1-MT-Vehicle), and 7 (ASXL1-MT-Rapamycin)). Representative FACS plot (b) and summarized data (c) are shown. d Cell cycle analysis with Ki-67/DAPI staining of LT-HSCs (n = 7 (Young control), 6 (Control-Vehicle), 7 (Control-Rapamycin), 5 (ASXL1-MT-Vehicle), and 7 (ASXL1-MT-Rapamycin)). e Apoptosis analyses of LT-HSCs (n = 5 (Control-Vehicle), 7 (Control-Rapamycin), 5 (ASXL1-MT-Vehicle), and 7 (ASXL1-MT-Rapamycin)). f The experimental design for treatment with an Akt inhibitor perifosine in aged mice. Aged Vav-Cre ASXL1-MT KI mice and age-matched control mice were treated with a single oral dose (36 mg/kg) of perifosine (n = 5). g 16 h after administration, cell cycle analyses with Ki-67/DAPI staining of LT-HSCs were performed. Statistical significances are assessed by one-way ANOVA with Tukey–Kramer’s post-hoc test. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001.

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