Fig. 6

Trisomy 21 contributes to increased sensitivity of CD43⁺ hematopoietic progenitor production to IGF inhibition. a Inhibition of IGF signaling by 1 μM PPP, an IGF inhibitor, has distinct effects on the CD34⁺ and CD43⁺ populations. Production of CD43⁺ early hematopoietic progenitor populations are more sensitive to IGF inhibition, whereas CD34⁺CD43⁻ hemogenic endothelium-enriched population is only slightly affected. b Analysis of the effects of IGF inhibition at three lower concentrations identifies the window of sensitivity for the CD43⁺ cells. Drug/no drug ratios were calculated by the percentage of each population in treated cultures divided by the percentage of each population in untreated cultures. c Trisomy silencing reduces the sensitivity of CD43⁺ cell production to IGF signaling inhibition, suggesting greater reliance of trisomic CD43⁺ progenitors on IGF signaling. Drug/no drug ratios were calculated as in b and dox/no dox ratios were calculated by the drug/no drug ratio of dox-treated samples divided by drug/no drug ratio of samples without dox, to reflect the increased reliance on IGF signaling in trisomic CD43⁺ hematopoietic progenitors. Error bars represent s.e.m. from three independent experiments and P values were calculated by Student t test; **P < 0.01, ***P < 0.001