Article abstract

Nature Immunology 10, 109 - 115 (2008)
Published online: 7 December 2008 | Corrected online: 9 April 2009 | doi:10.1038/ni.1680



There is a Corrigendum (May 2009) associated with this Article.

ADAR1 is essential for the maintenance of hematopoiesis and suppression of interferon signaling

Jochen C Hartner1,2, Carl R Walkley1,2,6, Jun Lu1,3 & Stuart H Orkin1,2,4,5

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.

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  1. Department of Pediatric Oncology, Dana-Farber Cancer Institute; Harvard Medical School, Boston, Massachusetts 02115, USA.
  2. Division of Hematology-Oncology, Children's Hospital Boston, Boston, Massachusetts 02115, USA.
  3. Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
  4. Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.
  5. Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA.
  6. Present address: St. Vincent's Institute of Medical Research, Princes Street, Fitzroy, Victoria 3065, Australia.

Correspondence to: Stuart H Orkin1,2,4,5 e-mail: stuart_orkin@dfci.harvard.edu

* In the version of this article initially published, the Cre-transgenic mouse is identified incorrectly as Tg(SV40-cre)1Jrg. The correct mouse strain should be Tg(SCL6E5-Cre)1Jrg, and the citation describing this mouse (ref. 29) should be as follows: Gothert, J.R. et al. In vivo fate-tracing studies using the Scl stem cell enhancer: embryonic hematopoietic stem cells significantly contribute to adult hematopoiesis. Blood 105, 2724–2732 (2005). The error has been corrected in the HTML and PDF versions of the article.

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