3163 – OCIAD2 IS ESSENTIAL FOR BONE MARROW HEMATOPOIETIC STEM AND PROGENITOR CELL MAINTENANCE

The OCIA (Ovarian Carcinoma Immunoreactive Antigen) domain-containing protein Asrij/OCIAD1 maintains mouse hematopoietic stem cell quiescence and prevents myeloproliferative disease. However, the role of its family member, OCIAD2, in mouse hematopoiesis is unidentified. We report that in steady-state bone marrow (BM) hematopoiesis HSPCs are enriched in OCIAD2 expression as compared to mature blood cells. We generated the first ociad2 knockout (KO) mice and show that they are viable and fertile, with diminished hematopoietic stem and progenitor cells (HSPCs) due to enhanced apoptosis. The persisting OCIAD2-independent HSPC of KO BM are predominantly quiescent. However, the reduced HSPC frequency is not reflected in the abundance of more differentiated BM hematopoietic cells as the persisting KO BM have uncompromised differentiation potential. Further, OCIAD family proteins interact with each other and the loss of one leads to enhanced expression of the other member. Hence, we hypothesize that increased expression of Asrij in OCIAD2 KO HSPCs and differentiated blood cells may mitigate the effects of OCIAD2 depletion in maintaining hematopoiesis. We provide a new mouse model supporting the notion that hematopoiesis is a robust process with multiple routes, and may help elucidate mechanisms of blood stem cell quiescence and hematopoietic homeostasis.