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快速激活造血干细胞。

Rapid activation of hematopoietic stem cells.

机构信息

The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, National Institute for Biotechnology in the Negev, The Ben-Gurion University of the Negev, 84105, Beer Sheva, Israel.

出版信息

Stem Cell Res Ther. 2023 Jun 6;14(1):152. doi: 10.1186/s13287-023-03377-6.

DOI:10.1186/s13287-023-03377-6
PMID:37280691
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10245525/
Abstract

Adult hematopoietic stem cells (HSCs) in the bone marrow (BM) are quiescent. Following perturbations, such as blood loss or infection, HSCs may undergo activation. Surprisingly, little is known about the earliest stages of HSCs activation. We utilize surface markers of HSCs activation, CD69 and CD317, revealing a response as early as 2 h after stimulation. The dynamic expression of HSCs activation markers varies between viral-like (poly-Inosinic-poly-Cytidylic) or bacterial-like (Lipopolysaccharide) immune stimuli. We further quantify dose response, revealing a low threshold, and similar sensitivity of HSCs and progenitors in the BM. Finally, we find a positive correlation between the expression of surface activation markers and early exit from quiescence. Our data show that the response of adult stem cells to immune stimulation is rapid and sensitive, rapidly leading HSCs out of quiescence.

摘要

骨髓中的成人造血干细胞(HSCs)处于静止状态。在受到诸如失血或感染等干扰后,HSCs 可能会被激活。令人惊讶的是,人们对 HSCs 激活的最早阶段知之甚少。我们利用 HSCs 激活的表面标志物 CD69 和 CD317 发现,刺激后仅 2 小时就出现了反应。病毒样(多聚肌苷酸-多聚胞苷酸)或细菌样(脂多糖)免疫刺激物的 HSCs 激活标志物的动态表达有所不同。我们进一步量化了剂量反应,发现 HSCs 和骨髓中的祖细胞具有低阈值和相似的敏感性。最后,我们发现表面激活标志物的表达与早期退出静止状态之间存在正相关。我们的数据表明,成年干细胞对免疫刺激的反应是迅速而敏感的,这会导致 HSCs 迅速脱离静止状态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b3/10245525/7fbb115550f3/13287_2023_3377_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b3/10245525/e4cda176c313/13287_2023_3377_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b3/10245525/510ab9a45c9b/13287_2023_3377_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b3/10245525/b2a581ab5285/13287_2023_3377_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b3/10245525/7fbb115550f3/13287_2023_3377_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b3/10245525/e4cda176c313/13287_2023_3377_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b3/10245525/510ab9a45c9b/13287_2023_3377_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b3/10245525/b2a581ab5285/13287_2023_3377_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27b3/10245525/7fbb115550f3/13287_2023_3377_Fig4_HTML.jpg

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本文引用的文献

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2
Flt3- and Tie2-Cre tracing identifies regeneration in sepsis from multipotent progenitors but not hematopoietic stem cells.Flt3- 和 Tie2-Cre 标记可识别败血症中的多能祖细胞而非造血干细胞的再生。
Cell Stem Cell. 2023 Feb 2;30(2):207-218.e7. doi: 10.1016/j.stem.2022.12.014. Epub 2023 Jan 17.
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Chronic viral infections persistently alter marrow stroma and impair hematopoietic stem cell fitness.
BST2通过ERK信号通路促进造血干细胞的激活。
Exp Hematol. 2024 Dec;140:104653. doi: 10.1016/j.exphem.2024.104653. Epub 2024 Oct 2.
慢性病毒感染持续改变骨髓基质,损害造血干细胞的功能。
J Exp Med. 2021 Dec 6;218(12). doi: 10.1084/jem.20192070. Epub 2021 Oct 28.
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IL-1 mediates microbiome-induced inflammaging of hematopoietic stem cells in mice.IL-1 介导微生物组诱导的小鼠造血干细胞炎症老化。
Blood. 2022 Jan 6;139(1):44-58. doi: 10.1182/blood.2021011570.
5
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