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The small molecule BMP inhibitor, dorsomorphin, induces cardiomyogenesis in mouse ES cells.

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posted on 06.08.2008, 01:34 by Jijun Hao, Marie A. Daleo, Clare K. Murphy, Paul B. Yu, Joshua N. Ho, Jianyong Hu, Randall T. Peterson, Antonis K. Hatzopoulos, Charles C. Hong

(A) Chemical structures of dorsomorphin (DM), a selective BMP inhibitor, and 676489, a DM analog which inhibits VEGF/VEGFR2, but not BMP signaling. (B) ES cells treated with dorsomorphin (DM) from day −3 to 2 formed large areas of contracting cardiomyocytes that expressed DsRed-Nuc under the α-MHC promoter by day 12 of differentiation (right), but DMSO-treated cells did not (left). Upper panels depict representative red fluorescence images. Lower panels show the corresponding bright-field images. (C, D) Dorsomorphin treatment resulted in strong increases in expression of cardiac markers Nkx2.5 (*p = 0.021, **p = 0.020, #p = 0.0013), and Myh6 (*p = 0.046, **p = 0.026). Q-PCR results represent relative expression normalized to that of DMSO-treated cells at Day 0. Measurements were from at least three independent experiments for each time-point.