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**5** 

*Japan* 

**Interferon Regulatory Factor-2 Regulates** 

**Hematopoietic Stem Cells in** 

Tomoko Kohno3 and Toshifumi Matsuyama3

*1Department of Safety Research on Blood and Biological Products,* 

*2Laboratory of Self Defense Gene Regulation, Tokyo Metropolitan* 

*3Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki,* 

Hematopoiesis is regulated by intrinsic gene-regulatory networks, ensuring the rapid production of differentiated blood cells for the immediate needs of embryos and generation of definitive hematopoietic stem cells (HSCs) that are required for life-long hematopoiesis. Homeostasis in bone marrow is dependent on the ability of HSCs to faithfully self-renew and to generate progenitor cells that undergo limited proliferation and give rise to terminally differentiated cells in the peripheral blood. HSCs are specialized to give rise to all elements of the blood system throughout life (Orkin & Zon, 2002, 2008a, 2008b) and are capable of self-renewal and differentiation into various lineages of the hematopoietic system to form all types of blood cells. Self-renewal is a tightly controlled process through which stem cells divide and generate daughter stem cells with properties identical to those of the mother cells. However, under certain conditions, HSCs differentiate into progenitor cells with less ability to self-renew. Since the discovery of stem cells, intense research aimed at understanding the genetic and molecular bases of self-renewal has identified candidate regulatory factors involved in the process of HSC self-renewal. These include cell-intrinsic regulators, such as transcription factors, signal transducers, cell-cycle inhibitors and surface receptors and cell-extrinsic regulators, such as the bone marrow niche and cytokines (He et

Interferon (IFN) is produced by cells of the immune system in response to challenges by agents, such as viruses, bacteria and tumor cells. IFNs suppress viral replication, have immunomodulatory activities and are used clinically to treat viral diseases and malignancies, such as chronic myeloid leukemia (CML)(Stark, 1998). Type I IFNs are induced by the genomes of many RNA viruses, and this induction can be mimicked by the double-stranded RNA mimetic polyinosinic-polycytidylic acid (poly [I:C]) (Darnell et al.

**1. Introduction** 

al., 2009).

Atsuko Masumi1, Shoichiro Miyatake2,

*National Institute of Infectious Diseases, Tokyo,* 

**Mouse Bone Marrow** 

*Institute of Medical Science, Tokyo,* 
