MLLT3 控制人类造血干细胞的自我更新和移植
Vincenzo Calvanese1,2, Andrew T Nguyen3, Timothy J Bolan3
1Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA. vincalv@gmail.com.
Nature
|November 29, 2019
概括
MLLT3 (AF9) 对于培养人类造血干细胞 (HSC) 的维持至关重要. 稳定MLLT3的表达使得可移植的HSC能够显著扩展,解决了再生医学中的一个关键挑战.
科学领域:
- 血液学
- 干细胞生物学
- 分子生物学
背景情况:
- 人类造血干细胞 (HSCs) 的自我更新尚不清楚.
- 在培养物中维持HSC功能的失败限制了它们的移植扩张.
研究的目的:
- 确定文化中高度细胞自我更新和维护的关键调节因素.
- 调查MLLT3 (AF9) 在人类HSC功能中的作用.
主要方法:
- 在人类HSC (胎儿,新生儿,成年人) 和培养物中对MLLT3表达的定量分析.
- 在造血干细胞和原始细胞 (HSPC) 中MLLT3的消耗和过度表达.
- 在体内 (小鼠模型) 评估HSPC维护,扩展和多系复制.
- 染色体免疫沉以确定MLLT3局部化和对基因素修饰的影响 (H3K79me2).
主要成果:
- 在人体HSC中MLLT3的表达很高,但在培养物中是低调的.
- 在实验室中,MLLT3的耗尽会影响可移植的HSPC的维持.
- 稳定MLLT3表达导致可移植的HSC扩张超过12倍.
- 在初级和二级接受者中,扩大的HSC显示出平衡的多系复制.
- MLLT3局部化到活跃的促进体,维持H3K79me2水平,并保留培养中的HSC转录程序.
结论:
- MLLT3作为一个关键的HSC维护因素.
- MLLT3将基因组修饰途径与HSC基因表达调节联系起来.
- MLLT3是扩大治疗移植的HSC的一个有希望的目标.
相关概念视频
01:19Multipotency of Hematopoietic Stem Cells
3.7K
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...
3.7K
01:01Regulation of Hematopoietic Stem Cells
3.8K
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...
3.8K
01:21Lineage Commitment
4.0K
Commitment is the process whereby stem cells:
4.0K
01:14Maintenance of the ES Cell State
2.6K
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...
2.6K
01:21Hematopoiesis
8.4K
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...
8.4K