Figure 3: Forced SON expression rescues the function of m⁶A deficient HSCs. See also Figure S3.

(A) NUMB expression in Mettl3 cKO HSCs with SON overexpression compared to Mettl3 cKO HSCs and WT (Mettl3 f/f) HSCs as quantified by immunofluorescence. EV: empty vector controls; n=3 independent experiments.

(B) MYC expression in Mettl3 cKO HSCs with SON overexpression compared to Mettl3 cKO HSCs as quantified by immunofluorescence. n=2 independent experiments.

(C) SON overexpression in Mettl3 cKO HSC rescues its symmetric commitment defect measured by NUMB symmetric high divisions. Above: representative immunofluorescence images of paired daughter cells stained with DAPI (blue), NUMB (red), and brightfield. Scale bar: 10μm. Below: percentages of doublet cells in each type of cell division. n=74 (WT HSC EV); n=113 (Mettl3 cKO EV); n=70 (Mettl3 cKO SON); P value was calculated using Chi-square test.

(D) Scheme of transplant strategy in (E).

(E) Quantification of the frequency of donor-derived cells was shown in the peripheral blood at 4-week post transplantation, n = 6–9. n represents number of mice. Representative of three independent experiments.

(F) Scheme of SON truncation mutants.

(G) Quantification of the frequency of donor-derived cells was shown in the bone marrow LSK population 16 weeks post transplantation. n=2–4, n represents number of mice. Representative of three independent experiments. Data in (A), (B), (E), (G) represent means ± s.e.m. , * represents p < 0.05. ^** represents p < 0.01. ^*** represents p < 0.001. ^**** represents p<0.0001. ns represents p > 0.05.