ADAR1 is essential for the maintenance of hematopoiesis and suppression of interferon signaling
Jochen C Hartner, Carl R Walkley, Jun Lu, Stuart H Orkin
Nature Immunology | NATURE PUBLISHING GROUP | Published : 2009
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..View full abstract
Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
Supported by the Leukemia and Lymphoma Society ( C. R. W.) and the Howard Hughes Medical Institute ( S. H. O.).