Fig. 4: In vivo dm-aKG promotes regeneration of the aged intestine by inducing PC renewal.
From: Old mitochondria regulate niche renewal via α-ketoglutarate metabolism in stem cells
a, Once daily dm-aKG treatment for 3 weeks increased the percentage of renewed PCs in aged (≥18-month-old) mice. Representative FACS plot for sorting PCs (left, 2% contour plot) and EdU+ analysis of sorted PCs (middle, histogram). Plot of the flow cytometry analysis of EdU+ PCs. A two-tailed, unpaired Student’s t-test (PBS, n = 3; aKG, n = 4) was used. Data are shown as the mean ± s.d. b, Notum expression in renewed (EdU+) and pre-existing (EdU−) PCs of aged (≥18-month-old) mice after 3 weeks of dm-aKG. A two-tailed, paired Student’s t-test (n = 4) was used. Data are shown as the mean ± s.d. Data were normalized to the dm-aKG− EdU− population. c, Relative body weight of aged (≥18-month-old) and young (3–4-month-old) mice treated once daily with dm-aKG or vehicle for 2 weeks, followed by a single 5-FU (100 mg kg−1) injection. The daily data points represent the mean. Young (3–4-month-old, circles) and old (≥18-month-old, squares) mice are shown; the coloured area between the dashed lines represents the 50% interquartile range. The daily weight of aged dm-aKG-treated mice was compared to aged controls with a two-tailed, unpaired Student’s t-test (n = 7). d, Prophylactic dm-aKG treatment reduced 5-FU-induced weight loss at day 5 after injection in aged (≥18-month-old) mice without adverse effects on young (4-month-old) mice. A two-tailed, unpaired Student’s t-test (n = 6) was used. Data are shown as the mean ± s.d. e, Left: quantification of cellular density in ileal villi (cells per µm). Data are shown as the mean ± s.d.; each data point shown represents a mouse. A two-tailed, unpaired Student’s t-test (n = 6) was used. Right: representative immunofluorescence staining of villi after 5-FU treatment for 5 days (grey, DAPI; blue, E-cadherin). Scale bar, 10 μm (e).
