Fig 2: The PLP compartment captures RT1(9a) early transformed cells.(A and B) Expression of RUNX1-RUNX1T1 chromatin immunoprecipitation sequencing targets (18) in (A) Kat2aWT cells and (B) Kat2aNULL RT1(9a) single-cell trajectories. (C) Flow cytometry analysis of RT1(9a) pseudo-time–associated hematopoietic cell surface markers in representative Kat2a WT and Kat2a NULL AML. Plots are gated on RT1(9a)/GFP+Kit+Sca1-CD34-PLP-like cells (see fig. S4H). (D and E) RNA velocity (25) plots of RT1(9a) preleukemia in the presence (D) and in the absence (E) of Kat2a. Color coding reflects the progenitor compartments defined in Fig. 3. tSNE, t-distributed stochastic neighbor embedding.

Fig 3: Metronomic DOX decreases EPC mobilization in tumor-bear-ing WT but not Redd1-/- mice. B16 melanoma-bearing WT and Redd1-/- mice were metronomically treated with DOX or intrave-nously injected with Ad-Redd1. (A) Representative dot plots of VEGFR-2+/CD34+ EPCs were obtained in peripheral blood of mice using flow cytometry. (B) The number of VEGFR-2+/CD34+ EPCs was quantified by flow cytometric analysis (n = 10 mice/group). ***P < 0.001; ns, not significant vs. control.

Fig 4: SM22a+CD34+ Stromal-Resident Progenitor Cells Involved in Endometrial RegenerationNormal C57BL/6 mice were subjected to induced menstruation, and mouse uteri were harvested at 0, 36, 72, and 96 h post-P4 withdrawal. Tissue sections underwent immunofluorescence staining, and DAPI was used to counterstain cell nuclei.(A and B) (A) Immunofluorescent staining of SM22a and CD34 in tissue sections, and (B) SM22a+CD34+ cells in the stroma and epithelium of the mouse uterus were quantified.(C and D) (C) Immunofluorescent staining of SM22a and E-cadherin in tissue sections, and (D) SM22a+E-cadherin+ cells in the stroma and epithelium of the mouse uterus were quantified.(E and F) Normal C57BL/6 mice (non-mT/mG) and sm22aCre:mT/mG mice were subjected to induced menstruation. (E) Representative images and (F) quantification of GFP+ cells in the stroma and endometrium of uterine frozen sections from sm22aCre:mT/mG mice at 0, 36, and 72 h post-P4 withdrawal.All of the data are presented as means ± SEMs; n = 5; **p < 0.01 and ***p < 0.001 (two-sided Student’s t test). Scale bars: 20 µm (A, C, and E).

Fig 5: SM22a+CD34+ Stromal Mesenchymal Cells Transdifferentiate into Epithelial Cells In vitro(A–D) SM22a+CD34+ stromal mesenchymal cells express KLF4.(A) FACS analyses and sorting of GFP+CD34+ stromal mesenchymal cells from the uteri of 2-month-old mT/mG reporter mice (WT) and SENP1smKO:mT/mG mice.(B) The percentage of CD34+/GFP+ cells was quantified.(C and D) (C) GFP+CD34+ and GFP+CD34- cells were subjected to immunofluorescence staining with KLF4, and (D) the percentage of KLF4+/CD34+ cells were quantified.(E and F) SM22a+CD34+ stromal mesenchymal cells transdifferentiation to epithelial cells. Sorted GFP+CD34+ and GFP+CD34- cells were cultured in the absence or presence of E2 (10 ng/mL) for 10 days. (E) Cells were subjected to immunostaining for vimentin and E-cadherin, and (F) the percentage of positive cells was quantified.(G and H) Endometrium formation analyses. GFP+CD34+ and GFP+CD34- cells were cultured in a Matrigel-precoated 24-well plate.(G) The cells were incubated 6–48 h to allow the formation of endometrial-like structures with lumens.(H) The number of endometrium formations was quantified based on phase and fluorescence images.All of the data are presented as means ± SEMs; n = 6; **p < 0.01 and ***p < 0.001 (two-sided Student’s t test).