Figure 3. HSPCs expressing two opposing functional cell states exist in the BM of patients with FA.

(A) “High-TP53” expressing HSPCs and “High-MYC” expressing HSPCs co-exist in the BM of patients with FA. The LogRatio of TP53 expression was divided by the LogRatio of MYC expression per cell, resulting in a gradient spanning from “High-TP53” expressing HSPCs to “High-MYC” expressing HSPCs. The expression of MYC and TP53 per cell is represented with a red or blue bar.

(B) Flow cytometric analysis confirming the co-existence of MYC and p53 expressing CD34+ cells from FA patients. FACS plot for gating CD34+ cells is shown in left panel. FACS plot for MYC and p53 expression in CD34+ cells is shown in right panel. Two seemingly exclusive populations of FA CD34+ cells were detected, one with high MYC levels (shaded green box) and the other with high p53 levels (shaded pink box) in comparison to healthy cells. A third population (shaded in orange box) in samples from FA patients co-expresses medium-high levels of MYC and p53 in comparison to healthy CD34+ cells. Data are from pooled BM samples of two healthy controls and eight FA patients.

(C) FACS plot (left panel) and quantitation (right panel) of DNA content showing high MYC expression in FA CD34+ cells during S and G2/M phases of the cell cycle. The data are from pooled healthy BM controls (n=2) and patients with FA (n=8).

Data in (C) are represented as box plots. p-values of <0.001 were considered extremely significant (***, ****). See also Supplementary Figure 3.