同时的NOD1和NOD2删除在造血干细胞和祖细胞促进长期的捐赠者化学反应
A A Hawkes1, S G Kasimsetty1, H Li2
1Department of Immunology and Microbiology, Scripps Research Institute, 10466 North Torrey Pines Rd, La Jolla, CA 92037.
Transplantation and cellular therapy
|February 4, 2026
概括
在捐赠者的造血干细胞和原生细胞 (HSPC) 中删除NOD1和NOD2可增强移植后的长期嵌合和长期嵌合. 这通过重新编程干细胞代谢而改善结果,而不会影响免疫功能.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 移植科学 移植科学
背景情况:
- 造血干细胞移植 (HSCT) 的成功受限于不良的捐赠细胞移植.
- 捐赠细胞移植受到干细胞内的炎症反应和鲜为人知的分子调节者的影响.
- NOD1和NOD2,模式识别受体,与无菌炎症有关,可能影响干细胞应激反应.
研究的目的:
- 为了确定NOD1和NOD2是否内在调节造血干细胞 (HSC) 复制.
- 阐明NOD1/2删除增强HSCT后的供体细胞持久性和嵌合的机制.
主要方法:
- 在小鼠HSPC中评估NOD1/2表达.
- 在同基因和异基因移植模型中评估了野生类型与NOD1/2双淘汰HSPC的复制效率.
- 进行了竞争性移植测定和转录基因分析,以评估细胞内在影响和潜在机制.
主要成果:
- HSPCs表达NOD1和NOD2,通过炎症刺激进行上调.
- 删除NOD1/2显著增强了多种组织中的供体细胞复合和长期的奇幻.
- NOD1/2淘汰赛HSPCs表现出代谢重编程,包括改变的线粒体代谢,炎症信号和氧化应激反应.
结论:
- NOD1和NOD2作为先天性免疫检查点,限制了供体HSPC的移植.
- 同时缺少NOD1/2通过代谢重编程增强了基因组和干细胞存活率.
- 针对NOD1/2信号提供了一种新的策略,以改善HSCT结果.
更多相关视频
11:59Detection of Residual Donor Erythroid Progenitor Cells after Hematopoietic Stem Cell Transplantation for Patients with Hemoglobinopathies
Published on: September 6, 2017
7.8K
11:16Preparation and Gene Modification of Nonhuman Primate Hematopoietic Stem and Progenitor Cells
Published on: February 15, 2019
8.1K
相关概念视频
Multipotency of Hematopoietic Stem Cells
3.9K
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...
3.9K
Regulation of Hematopoietic Stem Cells
4.1K
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...
4.1K
The Eukaryotic Promoter Region
18.8K
The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences. The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...
18.8K
The Eukaryotic Promoter Region
4.0K
4.0K
Adult Stem Cells
33.9K
Stem cells are undifferentiated cells that divide and produce more stem cells or progenitor cells that differentiate into mature, specialized cell types. All the cells in the body are generated from stem cells in the early embryo, but small populations of stem cells are also present in many adult tissues including the bone marrow, brain, skin, and gut. These adult stem cells typically produce the various cell types found in that tissue—to replace cells that are damaged or to continuously...
33.9K
Embryonic Stem Cells
32.5K
Embryonic stem (ES) cells are undifferentiated pluripotent cells, meaning they can produce any cell type in the body. This gives them tremendous potential in science and medicine since they can generate specific cell types for use in research or to replace body cells lost due to damage or disease.
32.5K
