Abstract
The deaminase ADAR1 edits adenosines in nuclear transcripts of nervous tissue and is required in the fetal liver of the developing mouse embryo. Here we show by inducible gene disruption in mice that ADAR1 is essential for maintenance of both fetal and adult hematopoietic stem cells. Loss of ADAR1 in hematopoietic stem cells led to global upregulation of type I and II interferon-inducible transcripts and rapid apoptosis. Our findings identify ADAR1 as an essential regulator of hematopoietic stem cell maintenance and suppressor of interferon signaling that may protect organisms from the deleterious effects of interferon activation associated with many pathological processes, including chronic inflammation, autoimmune disorders and cancer.