Hypoxia inducible factor-1 (HIF-1) is a critical transcription factor for the hypoxic response, angiogenesis, normal hematopoietic stem cell regulation, and cancer development. Importantly, HIF-1 is also a key regulator for immune cell activation. In order to determine whether HIF-1 is sufficient for developing MDS phenotypes, we generated blood specific inducible HIF-1 transgenic mice. Using Vav1-Cre/Rosa26-loxP-Stop-loxP (LSL) rtTA driver, stable HIF-1 can be induced in a doxycycline administration dependent manner. After induction, HIF-1-induced mice developed thrombocytopenia, leukocytopenia, macrocytic anemia, and multi-lineage dysplasia. We also found activation of both innate and adaptive immunity in HIF-1- induced mice compared to those from control mice. Taken together, these data suggest that HIF-1 is sufficient to trigger a variety of key MDS features SOURCE: Yoshihiro HayashiLaboratory of Oncology Tokyo University of Pharmacy and Life Sciences

Pluto Bioinformatics

GSE83988: HIF-1 activation is sufficient for the development of MDS