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. 2019 Mar 28;104(11):2164–2177. doi: 10.3324/haematol.2018.208660

Figure 1.

Figure 1.

Limited recovery of Notch1+/∆TAD mice after chemotherapeutic stress. (A) Experimental design of 5-fluorouracil (5-FU) injection. 5-FU (150 mg/kg) was injected intraperioneally into Notch1+/+ (WT) and Notch1+/∆TAD 5-week old mice on days 1 and 14. (B) Kaplan-Meier plot indicating survival of WT and Notch1+/∆TAD mice after 5-FU injection. Mice (n=5-9) were monitored daily until terminal analysis at day 28 after the first 5-FU injection. The statistical significance (P=0.01) between WT and Notch1+/∆TAD 5-FU-treated littermates was determined by the Mantel-Cox test. (C) Body weight of WT and Notch1+/∆TAD mice 9 days after 5-FU injection. (D) Red blood cell (RBC) and platelet (PLT) counts and hemoglobin (Hb) concentration were determined from peripheral blood of WT and Notch1+/∆TAD mice (n=5-9 mice/group) before (D0) and at days 4, 7 and 9 after 5-FU injection. (E) Numbers of hematopoietic stem cells (HSC) and Lin−Sca1+c−kit+ (LSK) progenitors in the bone marrow were analyzed 9 days after 5-FU injection. HSC were defined as Lin−c−kit+Sca1+CD150+CD48−cells. The numbers of each population are expressed as mean± standard deviation (SD). (F) Cytometric analysis of common lymphoid progenitors (CLP) in bone marrow from WT and Notch1+/∆TAD mice at day 14 after 5-FU injection. CLP were defined as Lin−c-kitlowSca1lowCD135+CD127+ (left panel). Absolute numbers of CLP from each mouse are expressed as mean± SD (right panel). (G, H) Cytometric analysis of early T-cell precursors (ETP) and double-negative 3 (DN3) cells in the thymus from WT and Notch1+/∆TAD mice at day 14 after 5-FU injection. ETP and DN3 populations were defined as Lin−c-kit+CD25+CD144+ (G) and Lin−CD4−CD8−CD44−CD25+ (H), respectively. Absolute numbers of ETP and DN3 cells from each mouse are expressed as mean± SD. (I) Representative images of the thymus from WT and Notch1+/∆TAD mice at day 14 after 5-FU injection. *P<0.05, **P<0.01, ***P<0.001. ICN: intracellular domains of Notch; TAD: transcriptional activation domain; RAM: RBP-J-associated molecule domain; ANK: ankyrin repeats.