Organismal Biosystems Laboratories
Laboratory of Stem Cell Biology and Developmental Immunology
Prof. NAGASAWA Takashi
Keywords：
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
Members
| Takashi Nagasawa (Professor) | nagasawa.takashi.fbs[at]osaka-u.ac.jp |
|---|---|
| Yoshiki Omatsu (Associate Professor) | omatsu.yoshiki.fbs[at]osaka-u.ac.jp |
| Kazumi Nagahara (Secretary) | nagahara[at]fbs.osaka-u.ac.jp |
You could probably reach more information of individual researchers by Research Map and researcher's search of Osaka-U.
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Q＆A
- 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)
2023
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）
2022
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）
2021
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）
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）
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）
2020
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）
2019
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）
2018
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）
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）
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）
2017
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）
2016
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）
2014
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 ）
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 ）
2013
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 ）
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）
2011
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 ）
2010
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 ）
2007
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 ）
2006
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 ）
2004
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 ）
2003
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 ）
2001
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 ）
1998
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 ）
1996
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 ）
1994
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.
Contact
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]fbs.osaka-u.ac.jp (Prof. Takashi Nagasawa)
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