Extended Data Fig. 4. Comparison of the effects of Zrsr2 loss versus Tet2 knockout or Sf3b1^K700E or Srsrf2^P95H mutations on hematopoietic stem and progenitor cells.

(a) Schema of competitive bone marrow (BM) transplantation assays. (b) Absolute number of CD45.2+ long-term HSCs (LT-HSCs), LSK, and MPPs in the bone marrow of CD45.1 recipient mice 16 weeks following pIpC (n=8-10 each). For box and whiskers plots throughout, bar indicates median, box edges first and third quartile values, and whisker edges minimum and maximum values. (c) Percentage of CD45.2⁺ LT-HSCs, LSK, CMP, MEP, and GMP cells in the BM of CD45.1 recipient mice 16-weeks following pIpC (n=8-10 per each). P value was calculated relative to the control group by a two-sided t-test. (d) Representative FACS plots of data in (c). (e) Number of methylcellulose colonies generated from 100 sorted LT-HSCs from mice with the indicated genotype. n=3 biologically independent experiments. Error bars, mean values +/− SEM. P-values by one-way ANOVA with Tukey’s multiple comparisons test. (f) Percentage of CD45.2⁺ cells in the blood of recipient mice from Zrsr2 knockout/Sf3b1^K700E/WT double mutant cells and relevant controls pre- and post-pIpC administration to recipient mice (n=10 each). P-values by two-way ANOVA with Tukey’s multiple comparisons test. Data in (b), (c), and (f) are shown as box-and-whisker plots where bar indicates median, box edges first and third quartile values, and whisker edges minimum and maximum values.