Impact of ARNT deletion on HSC function. (A) Competitive reconstitution analysis demonstrates enhanced reconstitution of irradiated recipients by KO BM (n = 4 ctrl donors, n = 33 recipients, n = 4 KO donors, n = 33 recipients). (B) Four months after reconstitution, we evaluated reconstitution of hematopoietic progenitors in recipient animals. (C) Secondary reconstitution reveals defects in long-term reconstitution in KO HSCs (n = 19 ctrl recipients, n = 15 KO recipients). (D) Four months after secondary transplantation, we assessed donor contribution to the hematopoietic progenitors and found diminished reconstitution of all progenitors. (E-F) Homing to the bone marrow (E) and spleen (F) is unaffected by loss of ARNT (n = 5 ctrl, n = 5 KO). (G) 5-FU myelosuppression assay shows diminished survival of KO animals (black) relative to control animals (red) (n = 13 ctrl, n = 13 KO). (H-I) KO animals exhibited enhanced mobilization of both c-Kit⁺ progenitors (H) and LSK cells (I) in the peripheral blood after 5-FU treatment (n = 10 ctrl, n = 10 KO). *P < .05, **P < .01.