The effects of IFNα are cell autonomous and specific to type 1 interferon signaling. (A) Peripheral blood WCC was reduced in IFNα-treated Jak2^VF chimeric mice compared with vehicle controls (12.5 ± 2.9 × 10⁶/L vs 8.3 ± 2.0 × 10⁶/L, respectively; P = .05) but not in IFNα-treated Ifnar1^−/−Jak2^VF chimeric mice compared with vehicle controls (16.5 ± 4.6 × 10⁶/L vs 15.1 ± 2.8 × 10⁶/L, respectively; P = .62). (B) Peripheral blood RCC was reduced in IFNα-treated Jak2^VF chimeric mice compared with vehicle controls (20.2 ± 0.8 × 10⁹/L vs 16.6 ± 0.7 × 10⁹/L, respectively; P = .02) but not in IFNα-treated Ifnar1^−/−Jak2^VF chimeric mice compared with vehicle controls (18.9 ± 1.2 × 10⁹/L vs 19.4 ± 1.2 × 10⁹/L, respectively; P = .81). (C) Spleen WCC was reduced in IFNα-treated Jak2^VF chimeric mice compared with vehicle controls (165 ± 8 × 10⁶ vs 215 ± 10 × 10⁶, respectively; P < .01) but not in IFNα-treated Ifnar1^−/−Jak2^VF chimeric mice compared with vehicle controls (181 ± 29 × 10⁶ vs 174 ± 8 × 10⁶, respectively; P = .83). (D) Spleen weight was reduced in IFNα-treated Jak2^VF chimeric mice compared with vehicle controls (298 ± 30 mg vs 410 ± 17 mg, respectively; P = .02); however, there was no difference in IFNα-treated Ifnar1^−/−Jak2^VF chimeric mice compared with vehicle controls (321 ± 41 mg vs 364 ± 12 mg, respectively; P = .36). (E) MEP differentiation was potentiated by IFNα treatment in Jak2^VF chimeric mice compared with vehicle controls (76.4 ± 1.7% vs 56.9 ± 4.4%, respectively; P < .01), but there was no effect in Ifnar1^−/−Jak2^VF chimeric mice compared with vehicle controls (53.4 ± 2.7% vs 51.3 ± 4.4%, respectively; P = .69). (F) GMP differentiation was impaired in IFNα-treated Jak2^VF chimeric mice compared with vehicle controls (17.1 ± 1.5% vs 31.7 ± 3.3%, respectively; P < .01), but there was no effect in IFNα-treated Ifnar1^−/−Jak2^VF chimeric mice compared with vehicle controls (30.4 ± 1.6% vs 29.6 ± 3.4%, respectively; P = .85). (G) Reduced total LT-HSC numbers in IFNα-treated Jak2^VF chimeric mice compared with vehicle controls (5040 ± 1502 vs 13 430 ± 2026, respectively; P = .01) but no effect in IFNα-treated Ifnar1^−/−Jak2^VF chimeric mice compared with vehicle controls (7662 ± 1843 vs 7849 ± 1237, respectively; P = .94). (H) Representative flow cytometry plots showing cell cycle in lineage^lowKit^highSca1⁺CD150⁺ Jak2^VF or Ifnar1^−/−Jak2^VF LT-HSCs from chimeric recipient mice. G0 (quiescent) cells are Ki-67^lowDNA²ⁿ, G1 cells are Ki-67⁺DNA²ⁿ, and SG2M cells are Ki67⁺DNA⁴ⁿ. (I) Quiescence in Jak2^VF HSCs was reduced after IFNα treatment compared with vehicle control (6.0 ± 1.2% vs 15.4 ± 3.4%, respectively; P = .04), but there was no difference in Ifnar1^−/−Jak2^VF HSCs with IFNα treatment or vehicle control (27.8 ± 4.5% vs 30.6 ± 7.3%, respectively; P = .75). (J) Actively cycling Jak2^VF HSCs increased after IFNα treatment compared with vehicle control (47.0 ± 2.1% vs 29.8 ± 2.9%, respectively; P < .01), but there was no difference in Ifnar1^−/−Jak2^VF HSCs after IFNα treatment compared with vehicle control (24.2 ± 3.4% vs 24.0 ± 2.4%, respectively; P = .96) (n = 4/group for each experiment, mean +/− standard deviation).