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. Author manuscript; available in PMC: 2019 Nov 8.
Published in final edited form as: Nature. 2019 May 8;569(7756):418–422. doi: 10.1038/s41586-019-1191-6

Figure 3. AAV6-miR-199a administration induces cardiomyocyte proliferation.

Figure 3

a, Schematic representation of the protocol for BrdU administration. b, Representative Ki67 immunohistochemistry images of the infarct border zone (BZ) 12 days after surgery, and relative quantification. The bottom panels are high magnification images of the indicated portions of the upper images. Data are mean±SEM; the number of animals per group is indicated. *P<0.05; t-test, two-sided. Scale bar: 100 µm. c, d, Representative images of BrdU (c) and phospho-histone H3 (d) immunostaining in the infarct border zone 12 days post MI, with relative quantifications. The bottom panels are high magnification images of the indicated portion of the upper image. Data are mean±SEM; the number of animals per group is indicated. *P<0.05; t-test, two-sided. Scale bar: 100 µm. e, Aurora B immunofluorescence images showing localization in midbodies (arrow) in AAV6-miR-199a treated animals, 12 days post MI. Scale bar: 20 µm. f, Distribution of the number of total and BrdU+ nuclei per CM in AAV6-Control- and AAV6-miR-199a-treated pigs 12 days after surgery. Data are mean±SEM of four pigs with at least 8 sections analysed per pig. g, Representative images of multinucleated CMs with BrdU+ nuclei. WGA: wheat germ agglutinin to stain CM sarcolemma. Scale bar: 100 µm. h, Connexin-43 (CX43, red) and phospho-histone H3 (pH3, blue-green) immunofluorescence representative images of AAV6-miR-199a-treated pig heart sections, 12 days after infarction. Scale bar: 100 µm. i, Representative immunohistochemistry images of GATA4-positive cells in AAV6-Control- and AAV6-miR-199a-injected pigs, 12 days after treatment. The bottom panels are high magnification images of the indicated portions of the upper images. j, quantification of cells showing GATA4 cytoplasmic localization. Data are mean±SEM; the number of animals per group is indicated. Quantification is from at least 7 high-resolution images acquired from at least 8 different regions of each heart. *P<0.05; t-test, two-sided. Scale bar: 100 µm.