Hartner Jochen C, Walkley Carl R, Lu Jun, Orkin Stuart H
Department of Pediatric Oncology, Dana-Farber Cancer Institute; Harvard Medical School, Boston, Massachusetts 02115, USA.
Nat Immunol. 2009 Jan;10(1):109-15. doi: 10.1038/ni.1680. Epub 2008 Dec 7.
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.
脱氨酶ADAR1可对神经组织的核转录本中的腺苷进行编辑，并且在发育中的小鼠胚胎的胎儿肝脏中是必需的。在这里，我们通过对小鼠进行诱导性基因破坏实验表明，ADAR1对于维持胎儿和成年造血干细胞均至关重要。造血干细胞中ADAR1的缺失导致I型和II型干扰素诱导转录本的全面上调以及快速凋亡。我们的研究结果表明，ADAR1是造血干细胞维持的重要调节因子以及干扰素信号的抑制因子，它可能保护生物体免受与许多病理过程相关的干扰素激活的有害影响，这些病理过程包括慢性炎症、自身免疫性疾病和癌症。
