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1H, quantified in Fig. 1I). Experimental and clinical studies in humans and animals indicate the presence of precursor cells within the heart that have the capacity to reconstitute and restore cardiac function in damaged myocardium [15, 16, 34]. To determine whether the small round ICs observed in our heart samples are potential cardiogenic http://www.selleckchem.com/products/CP-690550.html precursors, sections of NM or IHDM were immunostained for expression of c-kit and ��-SA (Fig. 2A). In NM, only occasional ICs showed strong signal for c-kit while negative for ��-SA (��3 cells in high power field at ��40 magnification). In contrast, a striking increase in c-kit+ cells (��12 cells per hpf) was observed in sections of IHDM mainly confined to ischemic zones. No signal for c-kit was detected in negative controls when anti-c-kit antibody was replaced with an isotype-matched nonspecific antibody (supporting information Fig. 4A) and a strong signal present in mouse neural stem cells (positive controls) (supporting information Fig. 4B). The majority of these c-kit+ cells are small round ICs that lack CD45 or VEGFR2 [17] (Fig. 2B, quantified in Fig. 2C) and are putative CSCs. In skeletal muscle and small intestinal http://www.selleck.cn/products/MLN8237.html epithelium, activated stem cells express Lin-28 [26, 27]. We therefore determined whether Lin-28 is expressed in IHDM and whether it colocalizes with c-kit by IF. Only a few Lin-28+ ICs cells were present in NM compared to IHDM, which showed an increased number of ICs positive for Lin-28, negative for ��-SA or CD45 or VEGFR2 (supporting information Fig. 5A�C5E, quantified in supporting information Table 2). No signal for Lin-28 was detected in IHDM when anti-Lin-28 antibody was replaced with an isotype-matched nonspecific antibody but a strong signal was seen in mouse neural stem cells (positive control) (supporting information Fig. 5D, 5E). Of particular interest, Lin-28 is detected in c-kit+ CSCs (�� 8 cells per hpf; Fig. 3A, quantified in Fig. 3B). We interpret c-kit+CD45?VEGFR2? http://www.selleckchem.com/products/XL184.html small round ICs that express Lin-28 as being activated resident CSCs. Immunoblotting confirmed increased expression of c-kit and Lin-28 in IHDM compared to NM (Fig. 3C, quantified in Fig. 3D). Gene expression was concordant with protein expression; transcripts of both markers were detected in NM, with a striking increase expression in IHDM (***p?