Interplay between the EMT transcription factors ZEB1 and ZEB2 regulates hematopoietic stem and progenitor cell differentiation and hematopoietic lineage fidelity
Fig 5
Maintenance of a single Zeb2 wt allele rescues PB cytopenia and severe differentiation defects in Zeb1/2 DKO HSPCs.
(A) Hemavet analysis showing that maintenance of a single wt Zeb2 allele in Zeb2Δ/+, Zeb1Δ/Δ (abbreviated Zeb2Δ/+) mice can rescue the HCT defects observed in Zeb1/2Δ/Δ DKO including RBC and HB levels as well as normalization of PLT (right) numbers. (B) Flow cytometric analysis of HSPCs from the BM showing that presence of single Zeb2 allele in Zeb2Δ/+ mice can also normalize LSK, LT-HSC (lin−cKit+Sca1+CD34−Cd135−), ST-HSC (lin−cKit+Sca1+Cd34+Cd135−), HPC (lin−cKit+Sca1−), CMP, GMP, and MEP HSPC numbers compared to defects observed in Zeb1/2Δ/Δ DKOs. (C) Representative flow cytometry plot of HSPCs. Bars in panels represent mean ± SD, n = 5 per group; *p < 0.05; **p < 0.01; ****p < 0.0001, Dunnett multiple comparisons test. Raw data behind graphs are included in D of S1 Data. DKO, double knockout; HB, hemoglobin; HCT, hematocrit; HSPC, hematopoietic stem and progenitor cell; PB, peripheral blood; PLT, platelet; RBC, red blood cell; wt, wild-type.