Graduate School of Frontier Biosciences, Osaka University

Japanese

Laboratory of Stem Cell Biology and Developmental Immunology

  Name Email TEL
Professor NAGASAWA, Takashi +81-6-6879-4606
Assistant Prof. OMATSU, Yoshiki +81-6-6879-7968

Research outline

We are studying how microenvironmental niches regulate behavior of hematopoietic stem cells (HSCs) and immune cells in the bone marrow.

We isolated a chemokine, CXCL12 (SDF-1/PBSF) as a molecule that stimulates the growth of B cell precursors (Nagasawa, T., et al. PNAS 1994) and have found its multiple physiological functions in development (Nagasawa, T., et al. Nature 1996). We have shown that the primary physiologic receptor for CXCL12 is CXCR4, which also functions as a coreceptor for strains of HIV-1 (Tachibana, K., et al. Nature 1998) and that CXCL12-CXCR4 signaling is essential for colonization of bone marrow by hematopoietic cells including hematopoietic stem cells (HSCs)(Ara, T., et al. Immunity 2003), colonization of gonads by primordial germ cells (PGCs) during ontogeny (Ara, T., et al. PNAS 2003), maintenance of a pool of HSCs in adult bone marrow (Sugiyama, T., et al. Immunity 2006), development of immune cells, including B cells (Nagasawa, T. Nat. Rev. Immunol. 2006), vascularization of the gastrointestinal tract and cardiogenesis (Tachibana, K., et al. Nature 1998).

In recent years, we have identified a population of reticular cells, which express CXCL12 at high levels, termed CXCL12 abundant reticular (CAR) cells within bone marrow (Sugiyama, T., et al. Immunity 2006) and indicated that CAR cells are adipo-osteogenic progenitors and function as the special microenvironment niches for HSCs, B cells and erythroid cells, and that CXCL12 and SCF produced by CAR cells maintain hematopoietic stem and progenitor cells (Omatsu, Y., et al. Immunity 2010). Recently, we found that the transcription factor Foxc1 was preferentially expressed in CAR cells in the marrow, enhancing CXCL12 and SCF expression and was essential for inhibiting adipogenic processes in CAR progenitors, and development and maintenance of the HSPC niche (Omatsu, Y., et al. Nature 2014). We are studying the roles of CXCL12-CXCR4 signaling and CAR cells in hematopoiesis to understand the spatiotemporal regulation of lymphohematopoiesis by environmental factors within bone marrow.

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Figure 1
The reticular cells with long processes, which express CXCL12 at high levels, termed CXCL12 abundant reticular (CAR) cells are adipo-osteogenic progenitors and function as niches critical for proliferation of HSCs and lymphoid and erythroid progenitors and maintenance of HSCs in an undifferentiated state. The transcription factor Foxc1 is preferentially expressed in CAR cells in the marrow and is essential for inhibiting adipogenic processes in CAR progenitors, and development and maintenance of the HSPC niche.


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