- Title
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Reinforcing one-carbon metabolism via folic acid/Folr1 promotes β-cell differentiation
- Authors
- Karampelias, C., Rezanejad, H., Rosko, M., Duan, L., Lu, J., Pazzagli, L., Bertolino, P., Cesta, C.E., Liu, X., Korbutt, G.S., Andersson, O.
- Source
- Full text @ Nat. Commun.
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a?f Single-plane confocal pictures of pancreata in control (a), actb2:folr1 (b), tp1:folr1 (c), pax6b:folr1 (d), and ela3l:folr1 (e) larvae on the Tg(ins:kaede);Tg(ins:CFP-NTR) background, following two days of ?-cell regeneration. TOPRO was used to counterstain nuclei, and the whole pancreas is outlined with a white dashed line. Quantification of the pancreatic ?-cells showed that actb2:folr1 and tp1:folr1 overexpression had comparable increases in the ?-cell regeneration assay (f). Scale bar, 10??m. n?=?17 (control), n?=?17 (actb2:folr1), n?=?15 (tp1:folr1), n?=?16 (pax6b:folr1), and n?=?16 (ela3l:folr1) biologically independent zebrafish larvae used for the quantification of ?-cells. Data are presented as mean values?±?SEM. One-way ANOVA was performed followed by Dunnett?s multiple comparison tests. f *P?=?0.0348 (control vs. actb2:folr1), *P?=?0.0202 (control vs tp1:folr1). g?j Single-plane confocal images of islets in control (g) and Tg(actb2:folr1) (h) larvae on the Tg(ins:H2BGFP);Tg(ins:flag-NTR) background following two days of ?-cell regeneration while incubated with EdU to label proliferating cells. Quantification showed an increase in ?-cell regeneration in the Tg(actb2:folr1) line (i), but no change in the number of ?-cells incorporating EdU was observed (j). Arrowheads point to EdU+ins:H2BGFP+ cells. Scale bar, 10??m. n?=?16 control and n?=?15 Tg(actb2:folr1) biologically independent zebrafish larvae were used for the quantification of this experiment. Data are presented as mean values?±?SEM. Unpaired two-tailed Student?s t test was used to assess significance. i *P?=?0.0122, j nonsignificant (ns), P?=?0.3943. k?n Single-plane confocal images of islets in control (k) and Tg(actb2:folr1) (l) larvae on the Tg(ins:H2BGFP);Tg(ins:flag-NTR);Tg(tp1:H2BmCherry) background, used to lineage trace the ductal cells of the pancreas, after ?-cell ablation. Quantification showed an increase in the number of regenerating ?-cells (m) colabeled with the ductal cell marker tp1:H2BmCherry (n). Arrowheads point to tp1:H2BmCherry+ins:H2BGFP+ cells. Data for m, n were pooled from two independent experiments. Scale bar, 10??m. n?=?20 control and n?=?21 Tg(actb2:folr1) biologically independent zebrafish larvae were used for the quantification of samples pooled from two independent experiments. Data are presented as mean values?±?SEM. Unpaired two-tailed Student?s t test was used to assess significance for (m) *P?=?0.0306. The Mann?Whitney two-tailed test was used for (n) ***P?=?0.0010. |
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