Organismal Biosystems Laboratories

Laboratory of Stem Cell Biology and Developmental Immunology

Prof. NAGASAWA Takashi Prof. NAGASAWA Takashi


Niche, Hematopoietic stem cells (HSCs), Mesenchymal stem cells, Bone marrow, B cell

Studying how microenvironmental niches develop and regulate hematopoietic stem cells (HSCs) and Immune cells

In recent years, we have identified a population of reticular cells which express chemokine CXCL12 at high levels, called CXCL12 abundant reticular (CAR) cells, within bone marrow. This indicated that CAR cells are mesenchymal stem cells and create special microenvironment niches essential for the maintenance of hematopoietic stem cells (HSCs), immune cells such as B cells, and erythroid cells. We have found that the transcription factors Foxc1, Ebf1/3, and Runx1/2 are preferentially expressed in CAR cells in the bone marrow and are essential for inhibiting adipogenic, osteogenic, and fibrogenic processes in CAR cells, respectively, and maintaining HSC niches. We are studying how CAR cells develop and control HSCs and hematopoiesis to understand the spatiotemporal regulation of lymph hematopoiesis within bone marrow.

The development, identity, and functions of CAR cells within the bone marrow


Takashi Nagasawa (Professor) nagasawa.takashi.fbs[at]
Yoshiki Omatsu (Associate Professor) omatsu.yoshiki.fbs[at]
Kazumi Nagahara (Secretary) nagahara[at]

You could probably reach more information of individual researchers by Research Map and researcher's search of Osaka-U.

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What is your hot research topic?
We are currently focusing on the development, functional molecular mechanism and disease related issue of niche that maintains tissue stem cells like hematopoietic stem cells etc.
What is your breakthrough or research progress ?
We identified the transcription factors that are specifically expressed in and play essential roles in cellular niches for HSCs.
Do you collaborate with other institutions and universities?
We are in collaboration with researchers in Harvard Medical School, the Univ. of Michigan and the Univ. of Zurich among others within Japan and around the world supplying model mice for research.
What kind of careers do your Lab's alumni go on to?
Principle Investigators within Japan and around the world, researchers at pharmaceutical companies, medical doctors etc.
How do you develop your research?
We will reveal the physiological role and functions of tissue stem cells and their niche.

Research Highlights

Publications (Research Articles, Reviews, Books)


Nakatani, T., Sugiyama, T., Omatsu, Y., Watanabe, H., Kondoh, G., Nagasawa, T.

Ebf3+ niche-derived CXCL12 is required for the localization and maintenance of hematopoietic stem cells

Nat. Commun. 37(3):109875  2023 PMID:37880234 DOI:10.1038/s41467-023-42047-2


Omatsu, Y., Aiba, S., Maeta, T., Higaki, K., Aoki, K., Watanabe, H., Kondoh, G., Nishimura, R., Takeda, S., Chung, Y., Nagasawa, T.

Runx1 and Runx2 inhibit fibrotic conversion of cellular niches for hematopoietic stem cells

Nat. Commun. 13(1):2654  2022 PMID:35551452 DOI:10.1038/s41467-022-30266-y


Nakagawa, T., Jorg, DJ., Watanabe, H., Mizuno, S., Han, S., Ikeda, T., Omatsu, Y., Nishimura, K., Fujita, M., Takahashi, S., Kondoh, G., Simons, BD., Yoshida, S., Nagasawa, T.

A multistate stem cell dynamics maintains homeostasis in mouse spermatogenesis

Cell Rep. 37(3):109875  2021 PMID:34686326 DOI:10.1016/j.celrep.2021.109875

Aoki, K., Kurashige, M., Ichii, M., Higaki, K., Sugiyama, T., Kaito, T., Ando, W., Sugano, N., Sakai, T., Shibayama, H., HANDAI Clinical Blood Club; Takaori-Kondo, A., Morii, E., Kanakura, Y., Nagasawa, T.

Identification of CXCL12-abundant reticular cells in human adult bone marrow

Br. J. Haematol. 193(3):659-668  2021 PMID:33837967 DOI:10.1111/bjh.17396

Sudo, T., Motomura, Y., Okuzaki, D., Hasegawa, T., Yokota, T., Kikuta, J., Ao, T., Mizuno, H., Matsui, T., Motooka, D., Yoshizawa, R., Nagasawa, T., Kanakura, Y., Moro, K., Ishii, M.

Group 2 innate lymphoid cells support hematopoietic recovery under stress conditions

J. Exp. Med. 218(5):e20200817  2021 PMID:33666647 DOI:10.1084/jem.20200817


Fukushima, K., Satoh, T., Sugihara, F., Sato,Y., Okamoto, T., Mitsui, Y., Yoshio, S., Li, S., Nojima, S., Motooka, D., Nakamura, S., Kida, H., Standley, M.D., Morii,E., Kanto,T., Yanagita,M., Matsuura, Y., Nagasawa, T., Kumanogoh, A., Akira,S.

Dysregulated Expression of the Nuclear Exosome Targeting Complex Component Rbm7 in Nonhematopoietic Cells Licenses the Development of Fibrosis

Immunity 52(3):542-556  2020 PMID:32187520 DOI:10.1016/j.immuni.2020.02.007


Sugiyama, T., Omatsu, Y., Nagasawa, T.

Niches for Hematopoietic Stem Cells and Immune Cell Progenitors

Int. Immunol. 31(1):5-11, 2019 Feb 6  2019 PMID:30169696 DOI:10.1093/intimm/dxy058


Mizuhashi, K., Ono, W., Matsushita, Y., Sakagami, N., Takahashi, A., Saunders, T.L., Nagasawa, T., Kronenberg, H.M., Ono, N.

Resting zone of the growth plate houses a unique class of skeletal stem cells.

Nature 563(7730):254-258  2018 PMID:30401834 DOI:10.1038/s41586-018-0662-5

Gomariz, A., Helbling, P.M., Isringhausen, S., Suessbier, U., Becker, A., Boss, A., Nagasawa, T., Paul, G., Goksel, O., Székely, G., Stoma, S., Nørrelykke, S.F., Manz, M.G., Nombela-Arrieta, C.

Quantitative spatial analysis of haematopoiesis-regulating stromal cells in the bone marrow microenvironment by 3D microscopy.

Nat. Commun. 9(1):2532  2018 PMID:29955044 DOI:10.1038/s41467-018-04770-z

Seike M, Omatsu Y, Watanabe H, Kondoh G, Nagasawa T

Stem cell niche-specific Ebf3 maintains the bone marrow cavity

Genes Dev. 32(5-6):359-372  2018 PMID:29563184 DOI:10.1101/gad.311068.117


Shimoto, M., Sugiyama, T., Nagasawa, T.

Numerous niches for hematopoietic stem cells remain empty during homeostasis.

Blood 129(15):2124-2131  2017 PMID:28130213 DOI:10.1182/blood-2016-09-740563


Cordeiro, Gomes, A., Hara, T., Lim, V.Y., Herndler-Brandstetter, D., Nevius, E., Sugiyama, T., Tani-Ichi, S., Schlenner, S., Richie, E., Rodewald, H.R., Flavell, R.A., Nagasawa, T., Ikuta, K., Pereira, J.P.

Hematopoietic Stem Cell Niches Produce Lineage-Instructive Signals to Control Multipotent Progenitor Differentiation.

Immunity 45(6):1219-1231  2016 PMID:27913094 DOI:10.1016/j.immuni.2016.11.004


Ono, N., Ono, W., Nagasawa, T., Kronenberg, H.M.

A subset of chondrogenic cells provides early mesenchymal progenitors in growing bones.

Nat. Cell Biol. 16(12); 1157-1167, 2014. Dec  2014 PMID:25419849 DOI:10.1038/ncb3067

Omatsu, Y., Seike, M., Sugiyama, T., Kume, T., Nagasawa, T.

Foxc1 is a critical regulator of haematopoietic stem/progenitor cell niche formation.

Nature 508; 536-540, 2014. Apr 24 Epub 2014 Mar 2.  2014 PMID:24590069 DOI:10.1038/nature13071


Bannard, O., Horton, R.M., Allen, C.D., An, J., Nagasawa, T., Cyster, J.G.

Germinal center centroblasts transition to a centrocyte phenotype according to a timed program and depend on the dark zone for effective selection.

Immunity 39(5); 912-924, 2013. Nov 14.  2013 PMID:24184055 DOI:10.1016/j.immuni.2013.08.038

Greenbaum, A., Hsu, Y.M.S., Day, R.B., Schuettpelz, L.G., Christopher, M.J., Borgerding, J.N., Nagasawa, T., Link, D.C.

CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance.

Nature 495(7440); 227-230, 2013 Mar 14  2013 PMID:23434756 DOI:10.1038/nature11926


Noda, M., Omatsu, Y., Sugiyama, T., Oishi, S., Fujii, N., Nagasawa, T.

CXCL12-CXCR4 chemokine signaling is essential for NK-cell development in adult mice.

Blood 117; 451-458, 2011. Jan 13.  2011 PMID:20944068 DOI:10.1182/blood-2010-04-277897


Omatsu, Y., Sugiyama, T., Kohara, H., Kondoh, G., Fujii, N., Kohno, K., Nagasawa, T.

The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche.

Immunity 33; 387-399, 2010. Sep 24.   2010 PMID:20850355 DOI:10.1016/j.immuni.2010.08.017


Kohara, H., Omatsu, Y., Sugiyama, T., Noda, M., Fujii, N., Nagasawa, T.

Development of plasmacytoid dendritic cells in bone marrow stromal cell niches requires CXCL12-CXCR4 chemokine signaling.

Blood 110; 4153-4160, 2007. Dec 15  2007 PMID:17827391 DOI:10.1182/blood-2007-04-084210


Sugiyama, T., Kohara, H., Noda, M., Nagasawa, T.

Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches.

Immunity 25; 977-988, 2006. Dec  2006 PMID:17174120 DOI:10.1016/j.immuni.2006.10.016


Tokoyoda, K., Egawa, T., Sugiyama, T., Choi, B.I., Nagasawa, T.

Cellular niches controlling B lymphocyte behavior within bone marrow during development.

Immunity 20; 707-718, 2004. Jun   2004 PMID:15189736 DOI:10.1016/j.immuni.2004.05.001


Ara, T., Tokoyoda, K., Sugiyama, T., Egawa, T., Kawabata, K., Nagasawa, T

Long-term hematopoietic stem cells require stromal cell-derived factor-1 for colonizing bone marrow during ontogeny.

Immunity 19; 257-267, 2003 (cover photo). Aug  2003 PMID:12932359 DOI:10.1016/s1074-7613(03)00201-2


Egawa, T., Kawabata, K., Kawamoto, H., Amada, K., Okamoto, R., Fujii, N., Kishimoto, T., Katsura, Y., Nagasawa, T.

The earliest stages of B cell development require a chemokine stromal cell-derived factor / pre-B cell growth-stimulating factor.

Immunity 15; 323-334, 2001. Aug   2001 PMID:11520466 DOI:10.1016/s1074-7613(01)00185-6


Tachibana, K., Hirota, S., Iizasa, H., Yoshida, H., Kawabata, K., Kataoka, Y., Kitamura, Y., Matsushima, K., Yoshida, N., Nishikawa, S., Kishimoto, T., Nagasawa, T.

The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract.

Nature 393 (6685); 591-594, 1998. Jun 11  1998 PMID:9634237 DOI:10.1038/31261


Nagasawa, T., Hirota, S., Tachibana, K., Takakura, N., Nishikawa, S.-I., Kitamura, Y.,Yoshida, N., Kikutani, H., Kishimoto, T.

Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1.

Nature 382 (6592); 635-638, 1996. Aug 15  1996 PMID:8757135 DOI:10.1038/382635a0


Nagasawa, T., Kikutani, H., Kishimoto, T.

Molecular cloning and structure of a pre-B-cell growth-stimulating factor.

Proc. Natl. Acad. Sci. USA. 91(6); 2305-2309, 1994. Dec  1994 PMID:8134392 DOI:10.1073/pnas.91.6.2305

Our ideal candidate (as a graduate student)

We are looking for a highly motivated person to work on our research topics as our lab member. Our lab welcomes the person who loves taking care of creatures, hand working and handcraft too. Any kind of background (such as your expertise or major) is available.


Laboratory of Stem Cell Biology and Developmental Immunology, Graduate School of Frontier Biosciences, Osaka University,
1-3 Yamadaoka, Suita, Osaka 565-0871 Japan.

TEL: +81-6-6879-4606

E-mail: tnagasa[at] (Prof. Takashi Nagasawa)

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