ARHGEF2 is significantly downregulated among differentially expressed genes in SDS HSCs. (A) ARHGEF2 transcript expression within single hematopoietic stem cell (HSC), common myeloid progenitor (CMP), megakaryocyte-erythroid progenitor (MEP), and multilymphoid progenitor (MLP) cells from CD34⁺ patient samples from normal (N, black) or SDS (S, blue) backgrounds. (B-C) ARHGEF2 transcript expression from individual patient samples within (B) HSC/MPP (FDR = 0.0029) and (C) CMP (FDR = 0.0087) populations. ND and SDS represent normal donor and SDS samples, respectively. Each data point represents a single cell. (D) Western blot validation of shRNAs targeting SBDS (top); ARHGEF2 overexpression (bottom). (E) qPCR assessment of SBDS and ARHGEF2 expression in human CD34⁺ HSPCs after SBDS knockdown (n = 5 CB samples); each sample is represented by a unique symbol. (F) Flow cytometric evaluation of early apoptosis levels upon concomitant SBDS knockdown and ARHGEF2 overexpression in K562 cells (n = 3 biological replicates evaluated at day 3 of in vitro cultures). Error bars represent standard error of the mean (SEM). EV represents empty vector; **P < .01; ***P < .001.