ETV2在血液内皮细胞命运承诺之前使用了血液内皮细胞基因增强剂
Jeffrey D Steimle1, Chul Kim2, Megan Rowton1
1Departments of Pediatrics, Pathology, and Human Genetics, University of Chicago, Chicago, IL 60637, USA.
Cell reports
|June 18, 2023
概括
研究人员在细胞命运确定过程中探索了转录因子ETV2 (Ets变体2). 他们发现,激活ETV2结合增强剂,而不仅仅是ETV2结合,驱动了血液内皮细胞的结合.
科学领域:
- 发育生物学是发展生物学.
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 细胞命运的决定涉及复杂的阶段:规范,承诺和分化.
- 由于捕捉短暂细胞状态的困难,理解这些不同的阶段是具有挑战性的.
- 转录因子ETV2对于血液内皮细胞的分化至关重要.
研究的目的:
- 调查ETV2在血液内皮细胞命运决定的不同阶段的精确作用和活性.
- 区分基底特征,承诺和差异化的分子事件.
- 确定驱动这些过程的关键转录性调节机制.
主要方法:
- 在孤立的心脏-血液内皮细胞原始体群体中分析ETV2活性.
- 染色体可访问性测试用于识别ETV2结合部位.
- 转录造型,以评估基因表达变化.
- 区分ETV2结合与增强剂激活.
主要成果:
- 在共同的祖先中,ETV2的表达和结合部位变得可访问.
- 最初的ETV2结合发生在Etv2位点,随后是特定增强剂的激活.
- 血液内皮结合与ETV2结合增强剂的一个子集的激活相关.
- 血液内皮细胞分化涉及广泛的新ETV2结合位点和基因调节网络的激活.
结论:
- 这项研究描述了细胞命运确定过程中ETV2依赖转录的不同阶段.
- 从ETV2结合过渡到ETV2结合增强剂的激活对于血液内皮细胞命运承诺至关重要.
- 这为了解早期血液和血管发育的转录控制提供了一个精细的模型.
相关概念视频
01:21Lineage Commitment
3.0K
Commitment is the process whereby stem cells:
3.0K
01:19Multipotency of Hematopoietic Stem Cells
3.2K
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...
3.2K
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
01:21Hematopoiesis
5.4K
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...
5.4K
01:24Regulation of Angiogenesis and Blood Supply
2.6K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K
01:34Production of Formed Elements
1.5K
Hemangioblasts are multipotent stem cells originating from the mesoderm. They give rise to hematopoietic stem cells (HSCs), which undergo hematopoiesis to produce all the formed elements of blood. This process is regulated by a complex network of hematopoietic growth factors, including transcription factors, growth factors, and cytokines. These factors stimulate the HSCs to divide and differentiate, though some HSCs remain undifferentiated to maintain a self-renewing pool.
Most HSCs commit to...
Most HSCs commit to...
1.5K