基因甲基化驱动血造干细胞在增殖性压力后衰老的表型
Hagai Yanai1, Taylor McNeely1, Saipriya Ayyar1
1Epigenetics and Stem Cell Unit, Translational Gerontology Branch, National Institute On Aging, NIH, 251 Bayview Blvd, Suite 100/10C220, Baltimore, MD, 21224, USA.
GeroScience
|October 10, 2024
概括
造血干细胞 (HSC) 的增殖可以加速衰老的表型. 增殖性压力会影响HSC功能和表观遗传修饰,导致与年龄相关的衰退.
科学领域:
- 血液学 血液学 血液学
- 免疫学 免疫学 免疫学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 衰老研究研究 衰老研究
背景情况:
- 造血干细胞 (HSC) 的衰老与免疫功能障碍,贫血和癌症有关.
- 高状细胞扩散对衰老表型的具体影响,特别是在压力下,尚未完全理解.
研究的目的:
- 调查强制HSC复制如何影响HSC衰老和相关的表型.
- 探索表观遗传机制,特别是DNA甲基化,这是由增殖驱动的HSC衰老的基础.
主要方法:
- 在体内使用循环低剂量甲 (5FU) 治疗诱导的HSC增殖.
- 评估HSC衰老表型,包括白细胞计数,祖先种群和干细胞功能.
- 分析了HSC中的DNA甲基化模式和DNA双链断裂.
主要成果:
- 增殖性压力诱导了老化表型,如改变白细胞计数和减少淋巴细胞原始体.
- HSCs积累了高Slamf1表达,并显示了降低的溶解潜力.
- DNA甲基化变化,包括促进体和非编码区域的改变,反映了分裂史和功能衰退.
- 持续的增殖压力导致DNA双链断裂,独立于功能衰退.
结论:
- 高细胞增殖可以驱动某些衰老表型,主要是通过像DNA甲基化这样的表观遗传变化.
- 这项研究强调了增殖性压力在HSC衰老中的作用及其对免疫系统的影响.
相关概念视频
Multipotency of Hematopoietic Stem Cells
3.0K
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...
3.0K
Regulation 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
Lineage Commitment
3.0K
Commitment is the process whereby stem cells:
3.0K
Hematopoiesis
5.1K
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...
5.1K
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
Maintenance of the ES Cell State
2.2K
The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
2.2K


