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. 2012 Feb 22;122(3):948–962. doi: 10.1172/JCI60455

Figure 7. DYRK1A dosage imbalance is correlated with NFAT pathway dysregulation in human and murine primary cells.

Figure 7

(A) Ratio of live cells treated with serial dilution of the Harmine inhibitor at 3 days (n = 3 per group) normalized on untreated cells. Mean ± SD. (B) Representative FACS plots, showing the effect of 5 μM harmine on a 3-day TPA-induced megakaryocytic differentiation of CMY. (C) Venn diagram showing the number of common genes dysregulated between treated or infected CMK and CMY cells during TPA-induced megakaryocytic differentiation. (D and E) Representative Western blots of DYRK1A, NFATC2, phospho-NFATC2 (P-NFATC2), and NFATC4 expression (D) in CD41-enriched spleen cells from euploid mice compared with that in Ts1Rhr mice (n = 2) and (E) in Gata1s mice (n = 2) compared with that in Gata1s/Ts1Rhr mice. (F) Gata1s/Ts1Rhr/MPL W515L triple mutant cells are less sensitive to the NFAT/calcineurin inhibitor cyclosporine A (CsA) than the non-trisomic Gata1s/MPL W515L cells in liquid culture. Mean ± SD (n = 5 per group). (G) Flow cytometry analysis of CD41 and CD42 populations derived from Ts1Rhr bone marrow progenitors infected with control or DYRK1A shRNA and treated for 3 days with cyclosporine A or vehicle. Percentages of live cells are indicated.