与克隆造血相关的TET2功能丧失阻碍了在造血干细胞和祖细胞中的IL1β介导的表观遗传重编程
J McClatchy1,2, R Strogantsev3, E Wolfe1,2
1Division of Oncological Sciences, Oregon Health & Science University, Portland, OR, USA.
Nature communications
|December 7, 2023
概括
介质素-1β (IL1β) 通过促进缺少Tet2的干细胞的自我更新来驱动克隆性血液形成 (CH). 准IL1信号可能为白血病前疾病提供早期干预.
科学领域:
- 血液学 血液学 血液学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 免疫学 免疫学 免疫学
背景情况:
- 克隆性血液形成 (CH) 涉及干细胞的优势,增加了血液癌症和心血管疾病的风险.
- Tet2突变定义了CHIP,一种与IL1β升高相关的条件,但IL1β的作用仍然不清楚.
研究的目的:
- 调查IL1β对Tet2缺血造血的作用及其作为早期干预目标的潜力.
主要方法:
- 使用了一种小鼠模型,在血造干细胞/原生细胞 (HSPC) 中进行了Tet2删除.
- 向野生型和Tet2缺乏的HSPC,老老鼠和人类祖先给予IL1β.
- 分析了DNA甲基化,与自我更新和分化相关的基因表达,以及单细胞/巨细胞群.
主要成果:
- 在缺乏Tet2的HSPC中,IL1β促进了亲炎性单细胞/巨细胞扩张,并降低了血统相关增强剂的脱甲基化.
- 在野生类型的HSPC中,IL1β诱导了DNA低甲基化,但在缺乏Tet2的HSPC中被抵抗.
- 通过对自我更新基因进行上调和保护与差异化相关的结合部位免受脱甲基化,IL1β增强了自身更新,并抵制了缺乏Tet2的HSPCs的分化.
结论:
- Tet2调解了一种由IL1β驱动的表观遗传程序,以平衡干细胞自我更新和分化.
- 针对IL1信号提供了一个潜在的早期干预策略,用于CHIP等白血病前疾病.
更多相关视频
10:33Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase
Published on: October 15, 2018
8.3K
11:40Retroviral Infection of Murine Embryonic Stem Cell Derived Embryoid Body Cells for Analysis of Hematopoietic Differentiation
Published on: October 20, 2014
8.5K
相关概念视频
01:01Regulation of Hematopoietic Stem Cells
3.2K
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
3.2K
01:21Lineage Commitment
3.0K
Commitment is the process whereby stem cells:
3.0K
01:19Multipotency of Hematopoietic Stem Cells
3.1K
The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
3.1K
01:24T Cell Types and Functions
1.0K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.0K
01:21Hematopoiesis
5.3K
The process of blood cell formation is called hematopoiesis. Hematopoiesis starts early during development, on the seventh day of embryogenesis. This phase of hematopoiesis is called the primitive wave, wherein the extraembryonic yolk sac allows the production of erythroid cells and endothelial cells from a common precursor called hemangioblast. The erythroid cells provide oxygen to support the growth of the rapidly dividing embryo. Hemangioblasts later develop into hematopoietic stem cells or...
5.3K