在调节性T细胞中丧失Y染色体
Jonas Mattisson1, Jonatan Halvardson1, Hanna Davies1
1Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
BMC genomics
|March 5, 2024
概括
白细胞中Y染色体 (LOY) 的马赛克损失在老年男性中很常见. 这项研究发现,调节性T细胞特别受到LOY的影响,可能会增加癌症风险.
科学领域:
- 遗传学 遗传学 是一个
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
背景情况:
- 染色体Y (LOY) 的马赛克损失是老年男性中最常见的体质形,与增加的死亡率和癌症风险有关.
- 以前的研究表明,LOY的影响因白细胞类型而异,前列腺癌患者的CD4+T细胞的LOY较高,尽管水平较低.
- 这项研究调查了特定的CD4+T淋巴细胞子集是否受到LOY的不成比例影响.
研究的目的:
- 为了研究 CD4+ T 淋巴细胞的特定子集受到Y染色体 (LOY) 的马赛克损失的影响.
- 确定LOY对T淋巴细胞分化和免疫功能的影响.
- 探索受LOY影响的调节性T细胞对癌症风险的潜在贡献.
主要方法:
- 对来自癌症患者 (肝,肺,结直肠) 的公开可用的,富含T淋巴细胞的单细胞RNA测序数据集的分析.
- 从PBMC和CD4+ T淋巴细胞丰富样本生成一个新的单细胞RNA测序数据集.
- 对T淋巴细胞子集的发育轨迹分析和基因表达造型.
主要成果:
- 与其他T淋巴细胞亚型相比,调控性T细胞的LOY显著更高.
- 调节性T细胞中的LOY导致调节性T细胞的比率增加,这表明对淋巴细胞分化的影响.
- 鉴定了受LOY影响的调节性T细胞中465个基因的失调,许多与免疫抑制和调节性T细胞发育有关.
结论:
- 调节性T细胞特别容易受到Y损失的影响,导致它们的丰富和免疫功能发生改变.
- 这种对LOY载体调节性T细胞的丰富可能导致LOY在白细胞中的男性观察到的癌症风险增加.
- 这些发现突出了一个特定的机制,通过免疫失调将LOY与癌症病原体联系起来.
相关概念视频
Loss of Tumor Suppressor Gene Functions
4.8K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.8K
The Y Chromosome Determines Maleness
6.6K
The Y chromosome is a sex chromosome found in several vertebrates and mammals, including humans. In addition to 22 pairs of autosomes, the human males have one X chromosome and one Y chromosome. In these organisms, the presence or absence of the Y chromosome determines the development of male traits.
Evolution
Around 300 million years ago, the two sex chromosomes diverged from two identical autosomal chromosomes. Over time, the Y chromosome has lost most of its genes, shrinking in size....
Evolution
Around 300 million years ago, the two sex chromosomes diverged from two identical autosomal chromosomes. Over time, the Y chromosome has lost most of its genes, shrinking in size....
6.6K
X-Inactivation
38.5K
The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.
38.5K
Inheritance of Chromatin Structures
6.2K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
6.2K
T 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
Epigenetic Regulation
31.1K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
31.1K


