造血干细胞和原始细胞的异质性是从胚胎内皮中继承的
Joey J Ghersi1,2,3, Gabriel Baldissera1,2,3, Jared Hintzen1,2,3
1Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT, USA.
Nature cell biology
|July 17, 2023
概括
斑马鱼的微RNA-128损失扩大了胚胎中的造血干细胞和原生细胞 (HSPC),使它们倾向于红色和淋巴细胞系. 这种微RNA调节Wnt和Notch信号,影响HSPC的发展和异质性.
科学领域:
- 发育生物学是发展生物学.
- 干细胞生物学 干细胞生物学
- 分子遗传学 分子遗传学
背景情况:
- 确定的造血干细胞和原始细胞 (HSPC) 对于生成所有血系至关重要.
- 在胚胎发育过程中,HSPCs起源于大动脉 - 淋巴体 - 半神经 (AGM) 区域的血源性内皮细胞.
- 在分化和扩散方面,HSPC异质性背后的机制仍然不太清楚.
研究的目的:
- 研究微RNA-128 (miR-128) 在调节HSPC发育和异质性的作用.
- 阐明miR-128如何影响胚胎HSPC细胞的细胞周期状态和血统承诺.
- 确定miR-128在血液形成过程中对Wnt和Notch信号通路的影响.
主要方法:
- 使用斑马鱼作为模型生物来研究HSPC的发展.
- 操纵的miR-128水平在分化血源性内皮细胞和观察到对HSPCs的影响.
- 采用人类多能干细胞来验证发现.
- 分析了Wnt和Notch信号通路组件,包括csnk1a1和jag1b.
主要成果:
- 斑马鱼中miR-128的损失导致AGM中HSPCs的扩张,细胞周期分布发生改变.
- miR-128 缺乏导致了对红细胞和淋巴细胞祖先的血统倾斜.
- 在分化的内皮细胞中操纵miR-128重复了这些效应在斑马鱼和人类细胞中.
- 发现miR-128抑制了Wnt抑制剂csnk1a1和Notch配体jag1b,从而促进了Wnt和Notch信号传递.
结论:
- 在HSPC的异质性源于大动脉 - 淋巴体 - 介质膜 (AGM) 内皮.
- 微RNA-128在编程HSPC异质性方面发挥着至关重要的作用.
- 由miR-128调节的Wnt和Notch信号通路是HSPC分化和扩散偏差的关键决定因素.
更多相关视频
14:37Directed Differentiation of Primitive and Definitive Hematopoietic Progenitors from Human Pluripotent Stem Cells
Published on: November 1, 2017
11.1K
09:00Hemogenic Endothelium Differentiation from Human Pluripotent Stem Cells in A Feeder- and Xeno-free Defined Condition
Published on: June 16, 2019
9.6K
相关概念视频
01:19Multipotency of Hematopoietic Stem Cells
3.1K
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...
3.1K
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
01:34Production 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
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
01:21Lineage Commitment
3.0K
Commitment is the process whereby stem cells:
3.0K
01:20Overview of Hematopoiesis
4.1K
Hematopoiesis, or blood cell production, is a vital biological process that begins early in embryonic development and continues throughout life. This process generates the various types of cells found in blood, including red blood cells, white blood cells, and platelets from hematopoietic stem cells (HSCs).
Developmental Phases of Hematopoiesis
Initially, HSCs are formed in the embryonic yolk sac, a critical site for early blood cell production. These stem cells subsequently migrate to other...
Developmental Phases of Hematopoiesis
Initially, HSCs are formed in the embryonic yolk sac, a critical site for early blood cell production. These stem cells subsequently migrate to other...
4.1K