Cross-organ HSC trafficking during definitive hematopoiesis formation

确定性造血形成过程中的跨器官 HSC 运输

• 批准号: 18J20690
• 负责人: 瀬崎 真衣子
• 金额: $ 1.79万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2018
• 资助国家: 日本
• 起止时间: 2018-04-25 至 2021-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-18J20690/
• 关键词: definitive hematopoiesis; hematopoietic stem cells; stem cell heterogeneity; bone marrow; HSC trafficking; 3D whole-organ imaging; lineage tracing; mathematical modeling; hematopoietic switching; deep-learning analysis; EC remodeling

In this study, the cellular and molecular mechanism of hematopoietic stem cell (HSC) trafficking that occurs during definitive hematopoiesis formation was investigated in the fetal to neonatal mouse. Single-cell RNA-sequencing of P2 HSCs isolated from the bone marrow, liver and spleen revealed HSC heterogeneity. PCA analysis showed 3 distinct clusters of HSCs with unique HSC marker expression (varying levels of cKit, Sca-1, CD150 mean fluorescence intensity) and differentially expressed genes. Our functional analysis via in vitro CFU-F and in vivo 10-cell transplantation into lethally irradiated mice revealed striking differences among these 3 groups in their ability to generate colonies and donor chimerism. We are now investigating the biological significance of these HSC groups and their contribution to adult hematopoiesis via lineage tracing and knock-out or knock-down studies.

在这项研究中，研究了在特定的造血形成过程中发生的造血干细胞(HSC)转运的细胞和分子机制。从骨髓、肝脏和脾分离的P2 HSC的单细胞RNA测序显示HSC的异质性。主成分分析显示3个不同的HSC聚集区，具有独特的HSC标志物表达(不同水平的cKit、SCA-1、CD150平均荧光强度)和差异表达的基因。我们通过体外CFU-F和体内10细胞移植对致死照射小鼠进行的功能分析显示，这三组小鼠在产生集落和供体嵌合体的能力方面存在显著差异。我们现在正在通过谱系追踪和基因敲除或敲除研究来研究这些HSC群体的生物学意义以及它们对成人造血的贡献。

项目成果

University of Zurich(スイス)

苏黎世大学（瑞士）

ヒト化骨髄を形成するヒト間葉系幹・前駆細胞の解析

形成人源化骨髓的人间充质干/祖细胞的分析

• 发表时间: 2020
• 作者: Hayashi Y#;Sezaki M#;Takizawa H*;瀬崎真衣子
• 通讯作者: 瀬崎真衣子

University of Cambridge(英国)

剑桥大学（英国）

Autophagy is dispensable for the maintenance of hematopoietic stem cells in neonates

• DOI: 10.1182/bloodadvances.2020002410
• 发表时间: 2021-03-13
• 期刊: BLOOD ADVANCES
• 影响因子: 7.5
• 作者: Hashimoto, Michihiro;Umemoto, Terumasa;Suda, Toshio
• 通讯作者: Suda, Toshio

Spatiotemporal coordination of HSC transit and bone marrow remodeling during early hematopoiesis (口頭)

早期造血过程中 HSC 运输和骨髓重塑的时空协调（口服）

• 发表时间: 2019
• 作者: Hayashi Y#;Sezaki M#;Takizawa H*;瀬崎真衣子;瀬崎真衣子
• 通讯作者: 瀬崎真衣子