2021 Fiscal Year Final Research Report
Gene regulatory network in cellular niches for hematopoietic stem cells
Project/Area Number |
19K06688
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 44020:Developmental biology-related
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Research Institution | Osaka University |
Principal Investigator |
Omatsu Yoshiki 大阪大学, 生命機能研究科, 准教授 (80437277)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | 造血幹細胞 / ニッチ / 間葉系細胞 / 転写因子 / 骨髄 |
Outline of Final Research Achievements |
Previous studies have identified some transcription factors essential for the development and functional maintenance of CAR cells (CXCL12-abundant reticular cells) that construct niches for hematopoietic stem cells in bone marrow. However, the mechanisms how the gene regulatory network of CAR cells is established and maintained has not been fully understood. In this study, we identified several novel transcriptional regulators that are highly expressed in CAR cells and may have important rolls for niche function, and generated conditional knockout mice. In these mice, Runx1/2 conditional knockout mice displayed severe fibrosis and hematopoietic defects in bone marrow. Thus, HSC cellular niches require Runx1 or Runx2 to prevent their fibrotic conversion and maintain HSCs and hematopoiesis in adults.
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Free Research Field |
幹細胞生物学
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Academic Significance and Societal Importance of the Research Achievements |
本研究により、CAR細胞に特異的に発現しその線維化を抑制することによって造血幹細胞の維持に必須の役割を果たす転写因子が同定された。この転写因子はそれぞれ造血幹細胞と骨芽細胞の発生に必須の遺伝子(Runx1とRunx2)としてよく知られていたものであったが、CAR細胞における線維芽細胞への変化を抑制するという機能が新たに解明された。また骨髄線維症においてはCAR細胞でRunx1/2の発現が低下することがその進展に関与すると推測されたため、Runx1/2遺伝子が疾患における新たな治療や診断の標的となる可能性がある。
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