Integrated Single-Cell Bioinformatics Analysis Reveals Intrinsic and Extrinsic Biological Characteristics of Hematopoietic Stem Cell Aging.
Integrated Single-Cell Bioinformatics Analysis Reveals Intrinsic and Extrinsic Biological Characteristics of Hematopoietic Stem Cell Aging.
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综合单细胞生物信息学分析揭示造血干细胞衰老的内在和外在生物学特征
DOI：
10.3389/fgene.2021.745786
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发表时间：
2021
影响因子：
3.7
通讯作者：
Huang H
中科院分区：
文献类型：
--
作者：
Zeng X;Li X;Shao M;Xu Y;Shan W;Wei C;Li X;Wang L;Hu Y;Zhao Y;Qian P;Huang H
造血干细胞（HSC）衰老伴随着自我更新能力的丧失、骨髓偏向分化和造血系统恶性肿瘤风险增加，是干细胞研究的一个重要焦点。然而，HSC 衰老的机制尚未完全阐明。在本研究中，我们将 HSC 的 3 个独立的单细胞转录组数据集整合在一起，并将 Stat3 和 Ifngr1 确定为凋亡偏向和炎症老化 HSC 的两个标记。此外，还通过定量 RT-PCR 鉴定并进一步验证了年轻和老年 HSC 之间常见的差异表达基因 (DEG)。功能富集分析显示，这些差异表达基因主要参与细胞周期和肿瘤坏死因子（TNF）信号通路。我们进一步发现，Skp2 诱导的信号通路（Skp2→Cip1→CycA/CDK2→DP-1）有助于衰老 HSC 快速过渡到 G1 期。此外，对HSC衰老的外在变化的分析表明，骨髓微环境中炎症基因的表达水平增加。集落形成单位测定表明，炎症细胞因子促进细胞衰老，而炎症途径的阻断可显着恢复衰老的 HSC 功能并增加 B 细胞输出。总的来说，我们的研究阐明了 HSC 衰老的生物学特征，我们确定的基因和通路可能是识别和恢复衰老 HSC 的潜在生物标志物和靶点。
Hematopoietic stem cell (HSC) aging, which is accompanied by loss of self-renewal capacity, myeloid-biased differentiation and increased risks of hematopoietic malignancies, is an important focus in stem cell research. However, the mechanisms underlying HSC aging have not been fully elucidated. In the present study, we integrated 3 independent single-cell transcriptome datasets of HSCs together and identified Stat3 and Ifngr1 as two markers of apoptosis-biased and inflammatory aged HSCs. Besides, common differentially expressed genes (DEGs) between young and aged HSCs were identified and further validated by quantitative RT-PCR. Functional enrichment analysis revealed that these DEGs were predominantly involved in the cell cycle and the tumor necrosis factor (TNF) signaling pathway. We further found that the Skp2-induced signaling pathway (Skp2→Cip1→CycA/CDK2→DP-1) contributed to a rapid transition through G1 phase in aged HSCs. In addition, analysis of the extrinsic alterations on HSC aging revealed the increased expression levels of inflammatory genes in bone marrow microenvironment. Colony formation unit assays showed that inflammatory cytokines promoted cellular senescence and that blockade of inflammatory pathway markedly rejuvenated aged HSC functions and increased B cell output. Collectively, our study elucidated the biological characteristics of HSC aging, and the genes and pathways we identified could be potential biomarkers and targets for the identification and rejuvenation of aged HSCs.
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影响因子：
16.6
作者：
Grover A;Sanjuan-Pla A;Thongjuea S;Carrelha J;Giustacchini A;Gambardella A;Macaulay I;Mancini E;Luis TC;Mead A;Jacobsen SE;Nerlov C
通讯作者：
Nerlov C
衰老诱导的 IL27Ra 信号传导损害造血干细胞。
影响因子：
20.3
作者：
He, Hanqing;Xu, Panglian;Wang, Jianwei
通讯作者：
Wang, Jianwei
影响因子：
29
作者：
Jung, Haiyoung;Kim, Mi Jeong;Choi, Inpyo
通讯作者：
Choi, Inpyo
DOI：
10.1084/jem.20111490
发表时间：
2011-12-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dykstra B;Olthof S;Schreuder J;Ritsema M;de Haan G
通讯作者：
de Haan G
影响因子：
14.8
作者：
Efremova, Mirjana;Vento-Tormo, Miquel;Vento-Tormo, Roser
通讯作者：
Vento-Tormo, Roser