原始细胞的表观遗传原始化决定了对Tet2突变的敏感性
Giulia Schiroli1,2,3, Vinay Kartha2,3,4, Fabiana M Duarte2,3,4
1Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
Nature communications
|May 21, 2024
概括
在Tet2突变之前细胞的独特表观遗传状态会影响克隆性血液形成 (CH) 的结果. 特定的分子特征,如Sox4,可以通过促进脱差和增加突变细胞生长来恶化CH.
科学领域:
- 血液学 血液学 血液学
- 癌症生物学 癌症生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 造血干细胞 (HSC) 突变导致克隆造血 (CH),这是一个具有不同临床结果的疾病.
- 了解恶性前期对于预测CH结果至关重要.
研究的目的:
- 研究Tet2突变前的细胞状态如何影响CH中前恶性表型.
- 确定影响CH进展和临床结果的分子因素.
主要方法:
- 利用一种可诱导的系统对髓状细胞原始体进行克隆分析.
- 在不同细胞分化阶段检查了表观遗传异质性和对Tet2突变的功能反应.
- 在初级颗粒细胞-巨原体 (GMP) 和HSC模型中验证的发现.
主要成果:
- 克隆在相似分化阶段的表观遗传特征是异质的,对Tet2突变的反应也不同.
- 细胞分化阶段影响Tet2突变反应,显示源细胞的表观基因组调节CH行为.
- Sox4被确定为一个风险因素,使细胞对Tet2无活化敏感,诱导脱差,改变新陈代谢,并增加体内克隆输出.
结论:
- 原始细胞的表观遗传特征可以使特定克隆在CH中占主导地位.
- 这解释了即使在CH中存在相同的遗传突变时也观察到的多样化的临床表型.
相关概念视频
Epigenetic Regulation
3.0K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.0K
Lineage Commitment
3.0K
Commitment is the process whereby stem cells:
3.0K
Methods of Nuclear Reprogramming
1.8K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
1.8K
Somatic to iPS Cell Reprogramming
2.2K
Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
2.2K
Cancers Originate from Somatic Mutations in a Single Cell
11.9K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
11.9K
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K


