Inhibition of G9a Histone Methyltransferase Converts Bone Marrow Mesenchymal Stem Cells to Cardiac Competent Progenitors

Figure 4

Acquisition of phase bright phenotype by BIX01294-treated MSCs. Phase-contrast images showing (a–d) BIX01294-treated MSCs that were subsequently incubated with CCM. By 48-hour exposure to CCM, BIX01294-treated MSCs (a) exhibited bursts of PBCs (asterisk), (b) which imaged in bright field at higher magnification appear as colony bursts. Subsequently, PBCs derived from BIX01294-treated MSCs spread throughout the cultures, as shown in the following (c) 4 days and (d) 2 weeks of CCM incubation. (e, f) Parallel MSC cultures incubated with CCM without prior treatment with BIX01294 displayed far fewer PBCs, as shown at 2 and 4 days of incubation, respectively. (g) Tabulation of PBC yields from MSC cultures pretreated in presence or absence of BIX01294, as estimated by counting low adherent cells released by brief EDTA exposure. Note that preexposure to BIX01294 generated significantly greater numbers of PBCs from MSC cultures when exposed to CCM (). The display of PBCs from the BIX01294 plus CCM-treated MSC cultures was similar to that (h) produced by cultures of atrial tissue.

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