| 研究課題/領域番号 |
22K16302
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| 研究種目 |
若手研究
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| 配分区分 | 基金 |
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| 審査区分 |
小区分54010:血液および腫瘍内科学関連
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| 研究機関 | 神戸大学 |
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研究代表者 |
Afroj Tania 神戸大学, 医学研究科, 学術研究員 (50913034)
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| 研究期間 (年度) |
2022-04-01 – 2024-03-31
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| 研究課題ステータス |
交付 (2022年度)
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| 配分額 *注記 |
2,860千円 (直接経費: 2,200千円、間接経費: 660千円)
2023年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
2022年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
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| キーワード | Hematopoietic stem cell / Humanized mice / Trained immunity / Aging / CHIP / Clonal hematopoiesis / Xenograft model |
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| 研究開始時の研究の概要 |
Hematopoiesis is considered as a life-long production house of immune cells and the integral component of trained immunity.
Notably, aging is coupled with functional derangements in immune cells and clonal hematopoiesis. The regulation of trained immunity in aging and clonal hematopoiesis (CHIP) is currently unknown. Here, I propose to uncover the regulatory mechanism of aging and CHIP pathogenesis by trained immunity, using humanized mouse models that are given several hematopoietic stress related to aging, hope to open a new dimension of “healthy aging”.
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| 研究実績の概要 |
In the original research proposal, the objective was to investigate the functional impact of induced trained immunity in aged hematopoietic stem cells (HSCs) and its role in the pathogenesis of clonal hematopoiesis of indeterminate potential (CHIP).
During FY2022, the focus was on establishing a humanized mouse model by transplanting human cord blood-derived HSCs. The initial step involved establishing a connection with a cord blood bank to acquire fresh samples of human cord blood. A protocol was then developed to obtain high-quality CD34+ HSCs through cell sorting. Additionally, several immunodeficient mouse models were carefully selected to assess their compatibility for human HSC transplantation and evaluate the survival rates of humanized mice. The survival of humanized mice with aging depends on selective mouse strains and HSCs engraftment. Following the transplantation of HSCs (CD34+) into the humanized mice, the differentiation of these cells into mature immune cells has been clearly characterized and delineated.
To achieve the research goals, investigations are underway to identify genetic mutations in the target genes of the sorted human cord blood HSCs (CD34+ cells).
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
3: やや遅れている
理由
Due to unforeseen circumstances, I made the decision to transfer my academic pursuits to Kobe university from Kyoto University. While I anticipated a seamless transition, there were several factors that contributed to the delay in my research progress including administrative procedure, adjusting new environment etc. Familiarizing myself with the new research facilities, building new relationships with faculty members and peers, and settling into a different academic culture took some time, which further impacted the progress of my research.
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| 今後の研究の推進方策 |
To further explore the implications of my project, I will introduce stress to the hematopoietic stem cell (HSC) compartment using various stimuli such as a fungal cell wall component, LPS (lipopolysaccharide), tumors, or drugs.
Subsequently, I will evaluate the effects of the immune response by investigating changes in the HSCs themselves. This analysis will involve examining alterations in cytokine production, evaluating modifications in myeloid effector functions such as phagocytosis and cytotoxic effects. These assessments will provide insights into how the trained immune response impacts HSC behavior.
Additionally, I plan to investigate the gene expression profile of HSCs using RNA-seq analysis. This approach will help unravel the underlying molecular mechanisms and pathways associated with the trained immune response in HSCs, specifically in the context of aging and blood malignancies.
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