从诱导的多能干细胞中对内皮细胞转化为造血细胞的发育调节
Rachel Wellington1,2,3,4, Xiaoyi Cheng5, Clyde A Campbell5
1Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WA, USA.
bioRxiv : the preprint server for biology
|October 10, 2024
概括
从诱导多能干细胞 (iPSC) 产生造血干细胞 (HSC) 是一个挑战. 这项研究表明,在内皮转化为血液构造转换 (EHT) 过程中抑制FGF信号,可以改善来自iPSC的HSC生成.
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
- 血液形成 血液形成 血液形成
背景情况:
- 造血干细胞 (HSC) 起源于通过内皮转化为造血干细胞 (EHT) 的血源性内皮 (HE).
- 从诱导多能干细胞 (iPSC) 产生功能性HSC仍然是再生医学的一个重大挑战.
- 在体外和体内控制EHT的分子机制的理解对于改善iPSC分化协议至关重要.
研究的目的:
- 在iPSC分化过程中绘制EHT单细胞动态图.
- 为了确定体外和体外EHT之间的转录差异.
- 发现调节EHT的联结体受体相互作用,并改善IPSC衍生的造血干细胞和原始细胞 (HSPC) 的生成.
主要方法:
- 单细胞RNA测序分析iPSC胚胎体分化过程中的EHT动态.
- 整合iPSC数据与人类胚胎数据集进行比较分析.
- 配体-受体相互作用映射以确定关键信号通路.
- 在斑马鱼和iPSC模型中,FGF信号的化学抑制和激动.
主要成果:
- 在iPSC EHT期间观察到内皮基因的不完全抑制.
- 增加的FGF23信号与体外和体内EHT之间的基因表达差异有关.
- 抑制FGF信号增强了斑马鱼和iPSC分化中的HSPC生成.
- FGF信号激应减少了造血输出.
结论:
- 来自iPSCs的单细胞EHT动态已被绘制,揭示了与体内发育的关键差异.
- FGF信号传递,特别是FGF23,在调节EHT和造血输出方面发挥着至关重要的作用.
- 调节FGF信号提供了一个有希望的策略,以增强用于治疗应用的iPSC衍生HSC的生成.
相关概念视频
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
01:19Multipotency 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
01:24Regulation of Angiogenesis and Blood Supply
2.5K
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...
2.5K
01:13Induced Pluripotent Stem Cells
21.8K
Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
21.8K
01:21Lineage Commitment
3.0K
Commitment is the process whereby stem cells:
3.0K
01:21Hematopoiesis
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