Extended Data Fig. 8: TDP-43 is an essential protein for skeletal muscle formation.
From: TDP-43 and RNA form amyloid-like myo-granules in regenerating muscle
Related to Fig. 3. a, Schematic of the approach used to knockout Tardbp and quantify C2C12 myoblast proliferation. b, Schematic of the isolation and fluorescence-activated cell sorting (FACS) of muscle stem cells from Pax7IREScreTardbpflox/WTRosa26tdTomato and Pax7IREScreTardbpWT/WTRosa26tdTomato mice. More than 125,000 muscle stem cells were collected per mouse from two populations defined in b as TdTom+ and TdTom++. c, Tardbp mRNA expression relative to Gapdh mRNA expression from isolated muscle stem cells from b. n = 4 independent experiments, each a mean of technical triplicates, from n = 2 mice. Unpaired, two-tailed Student’s t-test, *P = 0.0469. Data are mean ± s.d. d, Myofibre feret diameter frequency distribution in uninjured Pax7IREScreTardbpflox/WT mice compared to Pax7IREScreTardbpWT/WT controls. n = 3 mice, 600 myofibres were quantified per condition. e, Quantification of myofibre feret diameter shown in c. In the box plots, the horizontal bars show the mean, boxes show the 25th and 75th percentiles, whiskers show the minimum and maximum, individual myofibres are shown as dots. n = 3 mice, 600 myofibres per condition. Unpaired, two-tailed Student’s t-test, P = 0.5925; ns, not significant. f, Pax7+ muscle stem cell numbers in uninjured Pax7IREScreTardbpflox/WT mice compared to Pax7IREScreTardbpWT/WT controls. n = 3 mice. Unpaired, two-tailed Student’s t-test, P = 0.1963. Data are mean ± s.d. g, Schematic of TDP-43 depletion in Pax7+ muscle stem cells during muscle regeneration in Pax7IREScreTardbpflox/WT and Pax7IREScreTardbpWT/WT mice. Tmx, tamoxifen. h, Quantification of myofibre feret diameters from Fig. 3h at 10 DPI in muscle stem cells from Pax7IREScreTardbpflox/WT mice compared to wild-type controls. In the box plots, the horizontal bars show the mean, boxes show the 25th and 75th percentiles, whiskers show the minimum and maximum, individual myofibres are shown as dots. n = 489 myofibres from n = 3 mice per condition. Unpaired, two-tailed Student’s t-test, ****P = 2.3 × 10−30. i, Similar Pax7+ muscle stem cell numbers at 10 DPI in muscle stem cells from Pax7IREScreTardbpflox/WT haploinsufficient mice compared to wild-type controls. Data are mean ± s.d. from n = 3 mice. Unpaired, two-tailed Student’s t-test, P = 0.89.
