title: ADAR1 is essential for the maintenance of hematopoiesis and suppression of interferon signaling.
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.
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute; Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Jochen C
authors.initials: JC
authors.lastname: Hartner
authors.forename: Carl R
authors.initials: CR
authors.lastname: Walkley
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Orkin
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000235:genetics* / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D007178:Inbreeding; D007372:Interferons / Q000276:immunology*; D008099:Liver / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016601:RNA-Binding Proteins; D015398:Signal Transduction
chemical_list: D016601:RNA-Binding Proteins; D007372:Interferons; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase