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Phenotypical and functional characterization of mesenchymal stem cells in the spleen

Research Project

Project/Area Number 25292194
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Integrative animal science
Research InstitutionTokyo University of Science

Principal Investigator

GOITSUKA RYO  東京理科大学, 研究推進機構生命医科学研究所, 教授 (50301552)

Co-Investigator(Renkei-kenkyūsha) MATSUZAKI YUMI  島根大学, 医学部, 教授 (50338183)
KAWAI YASUHIRO  国立感染症研究所, 動物管理室, 研究員 (00416281)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2013: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Keywords間葉系細胞 / 幹細胞 / 脾臓 / 発生 / 再生 / 微小環境 / 免疫 / 分化 / 間葉系幹細胞 / 転写因子 / リンパ器官 / 再生医療 / ニッチ / 造血
Outline of Final Research Achievements

Tlx1 is a transcription factor essential for spleen organogenesis, and is preferentially expressed in cultured mesenchymal stem cells derived from postnatal spleen. To characterize mesenchymal stemr cells in the spleen, we generated a reporter mouse line in which the CreER-Venus cassette was knocked into the Tlx1 gene locus, with the ROSA26-tdTomato allele, which enables both visualization of Tlx1+ cells by Venus and their lineage-tracing by tdTomato. A majority of Tlx1+ cells was localized in the red pulp, and these cells did not express mature stromal cell markers, but express mesenchymal stem markers. Tlx1+ cells have an ability to differentiate into adipocytes, osteoblasts and chondrocytes in vitro, and are capable to differentiate nearly all of the mesenchymal cell components of the spleen. Thus, these findings indicate that the Tlx1+ cells function as a spleen-selective mesenchymal stem/progenitor cells, participating in the homeostatic maintenance of the adult spleen.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (36 results)

All 2016 2015 2014 2013 Other

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 6 results) Presentation (27 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Remarks (1 results)

  • [Journal Article] MEIS1-mediated transactivation of synaptotagmin-like 1 promotes CXCL12/CXCR4 signaling and leukemogenesis.2016

    • Author(s)
      Yokoyama T, Nakatake M, Kuwata T, Couiznet A, Goitsuka R, Tsutsumi S, Aburatani H, Valk PJ, Delwel R, Nakamura T.
    • Journal Title

      J Clin Invest.

      Volume: 印刷中 Issue: 5 Pages: 1664-1678

    • DOI

      10.1172/jci81516

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Loss of the Homeodomain Transcription Factor Prep1 Perturbs Adult Hematopoiesis in the Bone Marrow.2015

    • Author(s)
      Yoshioka K, Oda A, Notsu C, Ohtsuka T, Kawai Y, Suzuki S, Nakamura T, Mabuchi Y, Matsuzaki Y, Goitsuka R.
    • Journal Title

      PLoS One.

      Volume: 10(8) Issue: 8 Pages: e0136107-e0136107

    • DOI

      10.1371/journal.pone.0136107

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An asymmetric antibody repertoire is shaped between plasmablasts and plasma cells after secondary immunization with (4-hydroxy-3-nitrophenyl)acetyl chicken γ-globulin.2015

    • Author(s)
      Tashiro Y, Murakami A, Goizuka R, Shimizu T, Kishimoto H, Azuma T
    • Journal Title

      Int Immunol

      Volume: 12 Pages: 609-20

    • DOI

      10.1093/intimm/dxv040

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Promotion of crystalline cellulose degradation by expansins from Orysa sativa2015

    • Author(s)
      Seki, Y., Kikuchi, Y., Yoshimoto, R., Aburai, K., Kanai, Y., Ruike, T., Iwabata, K., Goitsuka, R., Sugawara, F., Abe, M., and Sakaguchi, K.
    • Journal Title

      Planta

      Volume: 241 Issue: 1 Pages: 83-93

    • DOI

      10.1007/s00425-014-2163-6

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of a Tlx1(CreER-Venus) knock-in mouse strain for the study of spleen development.2014

    • Author(s)
      Nakahara R, Kawai Y, Oda A, Nishimura M, Murakami A, Azuma T, Kaifu T, Goitsuka, R.
    • Journal Title

      Genesis.

      Volume: 52 Issue: 11 Pages: 916-923

    • DOI

      10.1002/dvg.22829

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Meis1 regulates epidermal stem cells and is required for skin tumorigenesis2014

    • Author(s)
      Okumura K, Saito M, Isogai E, Aoto Y, Hachiya T, Sakakibara Y, Katsuragi Y, Hirose S, Kominami R, Goitsuka R, Nakamura T and Wakabayashi Y.
    • Journal Title

      PLOS ONE

      Volume: 9 Issue: 7 Pages: e102111-e102111

    • DOI

      10.1371/journal.pone.0102111

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Homeodomain transcription factor meis1 is a critical regulator of adult bone marrow hematopoiesis.2014

    • Author(s)
      Ariki R, Morikawa S, Mabuchi Y, Suzuki S, Nakatake M, Yoshioka K, Hidano S, Nakauchi H, Matsuzaki Y, Nakamura T, Goitsuka R.
    • Journal Title

      PLoS One.

      Volume: 9 Issue: 2 Pages: 87646-87646

    • DOI

      10.1371/journal.pone.0087646

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Meis1 is required for the maintenance of postnatal thymic epithelial cells.2014

    • Author(s)
      Hirayama T, Asano Y, Iida H, Watanabe T, Nakamura T, Goitsuka R.
    • Journal Title

      PLOS One

      Volume: 9 Issue: 3 Pages: e89885-e89885

    • DOI

      10.1371/journal.pone.0089885

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 髄外造血ニッチとしての脾臓微小環境の形成機構2016

    • Author(s)
      後飯塚僚
    • Organizer
      福岡大学医学部再生医学研究所セミナー
    • Place of Presentation
      福岡大学医学部、福岡
    • Year and Date
      2016-02-24
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Transcription factor Tlx1 regulates cell migration of the spleno-pancreatic mesenchyme in spleen organogenesis.2015

    • Author(s)
      Toru Kasahara, Akihisa Oda, and Ryo Goitsuka
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌コンベンションセンター、札幌
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Overexpression of Tlx1 in situ causes extramedullary hematopoiesis in the adult spleen.2015

    • Author(s)
      Akihisa Oda, Chihiro Notsu, and Ryo Goitsuka
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌コンベンションセンター、札幌
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Maintenance of the white pulp architecture in the postnatal spleen requires Meis1 expression in mesenchymal progenitor cells.2015

    • Author(s)
      Chihiro Notsu, Akihisa Oda, and Ryo Goitsuka
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌コンベンションセンター、札幌
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] n asymmetric antibody repertoire is shaped between plasmablasts and plasma cells after secondary immunization with (4-hydroxy-3-nitrophenyl acetyl; NP) hapten.2015

    • Author(s)
      Yasuyuki Tashiro, Akikazu Murakami, Ryo Goitsuka, Takeyuki Shimizu, Hidehiro Kishimoto and Takachika Azuma
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌コンベンションセンター、札幌
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Endogenous MOZ was essential for MOZ-TIF2-induced Meis1 upregulation and AML development.2015

    • Author(s)
      Katsumoto, T., Yamagata, K., Ogawara, Y., Nakamura, T., Goitsuka, R., and Kitabayashi, I
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      ホテル日航金沢(石川県)
    • Year and Date
      2015-10-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] Cell fate mapping of embryonic spleen primordium cells expressing the transcription factor Tlx1.2015

    • Author(s)
      Kasahara, T., Oda, A., and Goitsuka, R
    • Organizer
      第24回日本バイオイメージング学会学術集会
    • Place of Presentation
      東京理科大学葛飾キャンパス、東京
    • Year and Date
      2015-09-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] ホメオドメイン転写因子Tlx1は脾臓原基間葉系細胞の分化運命を規定する。2015

    • Author(s)
      笠原透、中原亮、野津智尋、小田朗永、後飯塚僚
    • Organizer
      第25回学術集会Kyoto T cell conference
    • Place of Presentation
      京都大学芝蘭会館(京都)
    • Year and Date
      2015-05-15 – 2015-05-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] ホメオドメイン転写因子Tlx1は赤脾髄における赤芽球・マクロファージの維持に関与する2015

    • Author(s)
      小田朗永、笠原透、野津智尋、後飯塚僚(
    • Organizer
      第25回学術集会Kyoto T cell conference
    • Place of Presentation
      京都大学芝蘭会館(京都)
    • Year and Date
      2015-05-15 – 2015-05-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] メオドメイン転写因子Tlx1は脾臓原基間葉系細胞の分化運命を規定する2015

    • Author(s)
      笠原透、中原亮、野津智尋、小田朗永、後飯塚僚
    • Organizer
      第25回学術集会Kyoto T cell conference
    • Place of Presentation
      京都大学芝蘭会館、京都
    • Year and Date
      2015-05-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] ホメオドメイン転写因子Tlx1は赤脾髄における赤芽球・マクロファージの維持に関与する2015

    • Author(s)
      小田朗永、笠原透、野津智尋、後飯塚僚
    • Organizer
      第25回学術集会Kyoto T cell conference
    • Place of Presentation
      京都大学芝蘭会館、京都
    • Year and Date
      2015-05-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] Contribution of Tlx1-expresssing mesenchymal cells to splenic microenvironment formation during organogenesis and regeneration.2015

    • Author(s)
      Akihisa Oda, Ryo Nakahara, Chihiro Notsu, and Ryo Goitsuka
    • Organizer
      Venice Thymus Meeting 2015
    • Place of Presentation
      Venice International University (Venice)
    • Year and Date
      2015-04-09 – 2015-04-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] Contribution of Tlx1-expressing mesenchymal cells to splenic microenvironment formation during organogenesis and regeneration.2015

    • Author(s)
      Akihisa Oda, Ryo Nakahara, Chihiro Notsu, Toru Kasahara, and Ryo Goitsuka
    • Organizer
      Venice Thymus Meeting 2015
    • Place of Presentation
      Venice International University, Italy
    • Year and Date
      2015-04-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] sotype-specific regulation of antibody secretion and affinity maturation during immune response to (4-hydroxy-3-nitrophenyl acetyl; NP) hapten.2014

    • Author(s)
      Yasuyuki Tashiro, Ryo Goitsuka and Takachika Azuma
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] The role of postnatal mesenchymal cell population retaining a potential to give rise to various types of mature stromal cells in the spleen.2014

    • Author(s)
      Akihisa Oda, Ryo Nakahara, Chihiro Notsu, Toru Kasahara, and Ryo Goitsuka
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Contribution of Tlx1-expresssing mesenchymal cells to splenic microenvironment formation during organogenesis and regeneration.2014

    • Author(s)
      Ryo Nakahara, Chihiro Notsu, Akihisa Oda, and Ryo Goitsuka
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] eis1 is a crucial regulator of epidermal stem cell maintenance and skin carcinogenesis2014

    • Author(s)
      Yuichi Wakabayashi, Kazuhiro Okumura, Megumi Saito, Yoshimasa Aoto, Yasubumi Sakakibara, Ryo Kominami, Ryo Goitsuka, Takuro Nakamura, and Eriko Isogai
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Role of Meis1 in the cerebellar development2014

    • Author(s)
      Tomoo Owa, Shinichiro Taya, Tomoki Nishioka, Takuro Nakamura, Ryo Goitsuka, Kozo Kaibuchi, Mikio Hoshino
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 脾臓の微小環境を構成する間葉系細胞の起源と機能2014

    • Author(s)
      後飯塚僚
    • Organizer
      第157回日本獣医学会学術集会
    • Place of Presentation
      北海道大学高等教育推進機構(札幌)
    • Year and Date
      2014-09-09 – 2014-09-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] 成体脾臓微小環境の維持におけるTlx1発現間葉系細胞の役割.2014

    • Author(s)
      小田朗永、野津智尋、中原亮、後飯塚僚
    • Organizer
      第24回学術集会Kyoto T cell conference
    • Place of Presentation
      京都平安ホテル(京都)
    • Year and Date
      2014-05-16 – 2014-05-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] Homeodomain transcription factor Tlx1 marks a unique population of postnatal spleen mesenchymal cells.2013

    • Author(s)
      Nakahara, R., Kawai, Y., Hirayama, T., Iwakura, Y. and Goitsuka, R
    • Organizer
      International Workshop on T Lymphocytes
    • Place of Presentation
      Kyoto
    • Related Report
      2013 Annual Research Report
  • [Presentation] A new mouse line for dissecting the lineage relationship and functions of mesenchymal cell components consisting of the spleen microenvironment.2013

    • Author(s)
      Goitsuka, R.
    • Organizer
      International Workshop on T Lymphocytes
    • Place of Presentation
      Kyoto
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Differentiation potentials of mesenchymal cells expressing the homeodomain transcription factor Tlx1 in embryonic and postnatal spleen.2013

    • Author(s)
      Goitsuka, R., Nakahara, R., Oda, A. and Notsu
    • Organizer
      4th Workshop of Synthetic Immunology
    • Place of Presentation
      Kyoto
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Mesenchymal progenitor-like cells in the neonatal spleen identified by homeodomain transcription factor Tlx1.2013

    • Author(s)
      Notsu, C., Oda, A., Nakahara, R. and Goitsuka, R.
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] Perivascular mural cells in the postnatal spleen express homeodomain transcription factor Tlx1.2013

    • Author(s)
      Nakahara, R., Oda, A. and Notsu, C., and Goitsuka, R.
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] Developmental regulation of the splenic microenvironment by mesenchymal cells expressing homeodomain transcription factor Tlx1.2013

    • Author(s)
      Oda, A., Notsu, C., Nakahara, R. and Goitsuka, R.
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] Homeodomain transcription factor Tlx1 marks a unique population of postnatal spleen mesenchymal cells.2013

    • Author(s)
      Nahara, R., Oda, A. and Notsu, C., and Goitsuka, R.
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      幕張
    • Related Report
      2013 Annual Research Report
  • [Remarks] 東京理科大学 生命医科学研究所/大学院 生命科学研究科 発生及び老化研究部門

    • URL

      http://www.ribs.tus.ac.jp/laboratories/block05/

    • Related Report
      2014 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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