中年期中介细胞KITL/SCF和IGF1表达的变化是稳定状态造血干细胞衰老的基础
Kira A Young1, Maria A Telpoukhovskaia1, Johanna Hofmann2,3
1The Jackson Laboratory, Bar Harbor, ME.
Blood
|April 10, 2024
概括
造血干细胞 (HSC) 的衰老表现出个体差异. 介酶体 stromal 细胞 (MSC) 信号传递,特别是基特配体 (KITL) 和类似胰岛素的生长因子1 (IGF1),独立于炎症影响 HSC 的衰老.
科学领域:
- 血液学 血液学 血液学
- 免疫学 免疫学 免疫学
- 衰老研究研究 衰老研究
- 干细胞生物学 干细胞生物学
背景情况:
- 造血衰老受到内在程序和外在因素,如炎症的影响.
- 在个体中血液形成衰老的表型中存在显著的异质性.
- 血液造血干细胞 (HSC) 中这种异质性的分子基础仍然不太清楚.
研究的目的:
- 为了研究在血液构成衰老中异质性的分子基础.
- 为了确定外在因素和细胞类型,预测HSC衰老特征的变化.
- 为科学界提供网上可访问的转录资源.
主要方法:
- 从年轻和中年老鼠中生成了血造细胞和非血造细胞的单个单细胞转录形状.
- 计算定义的分子模块用于中年HSC.
- 询问了外部细胞类型和预测HSC特征变异的因素.
主要成果:
- 造血干细胞 (HSC) 在中年老鼠中显示出扩张的最大表型变异.
- 介质干细胞 (MSCs) 的信号传递下降,特别是干细胞连接体 (KITL) 和类似胰岛素的生长因子1 (IGF1),最受影响的是中年 HSC 转录组.
- 较低的MSC Kitl和Igf1表达与减少的淋巴细胞系承诺和增加的分化不活跃的HSC相关,独立于炎症.
结论:
- 在中年老鼠中,基特连接体 (KITL) 和胰岛素类生长因子1 (IGF1) 表达是同调和变化的.
- 来自MSC的KITL和IGF1信号预测HSC激活和淋巴结合.
- 这种调节独立于与衰老相关的前炎性细胞因子发生.
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