血液构造结构的逐步破坏从克隆性血液构造到MDS
Michèle C Buck1, Lisa Bast2,3, Judith S Hecker1
1Technical University of Munich (TUM), School of Medicine, Department of Medicine III, Munich, Germany.
iScience
|July 31, 2023
概括
不确定潜力的克隆性血液形成 (CHIP) 涉及改变的血细胞发育. 计算建模显示,CHIP和骨髓质疏松综合征 (MDS) 能够重组造血层次结构,即使是在早期的癌前阶段.
科学领域:
- 血液学 血液学 血液学
- 计算生物学 计算生物学
- 遗传学 是一个遗传学.
背景情况:
- 不确定潜力的克隆性血液形成 (CHIP) 是血液形成干细胞/原始细胞 (HSPC) 中与年龄相关的体质突变的获取.
- 已知CHIP突变是骨髓质恶性瘤的驱动因素,例如骨髓质疏松综合征 (MDS).
- 目前尚不清楚CHIP和MDS中的克隆扩张是由于细胞动力学的改变还是由于血液构造层次的重组.
研究的目的:
- 在健康个体,CHIP和MDS中研究血造干细胞/原始细胞 (HSPC) 的动态变化和层次组织.
- 为了确定是否改变细胞动力学或等级重组驱动这些条件下的克隆扩张.
主要方法:
- 计算机建模用于分析培养的造血干细胞 (HSC) 的分化和增殖动力学.
- 从8名健康人群,7名CHIP患者和10名MDS患者获得样本.
- 分析的重点是用标准和替代的造血层次模型来解释HSPC动态.
主要成果:
- 标准的造血层次仅在健康样本中充分解释HSPC动力学.
- 需要替代层次来最好地描述57%的CHIP和70%的MDS样本中的动力学.
- 在CHIP和MDS中观察到各种HSPC区间的放松动力学,在CHIP和MDS中观察到显著的个体间异质性,而改变的HSC率在MDS中最为突出.
结论:
- 即使在癌前的CHIP状态下,HSPC区的重组也是一个可检测的特征.
- 这些发现突显出CHIP和MDS中显著的动力异质性和层次变化.
- 计算建模为解剖血液形成中的复杂细胞动态提供了一个强大的工具.
相关概念视频
Lineage Commitment
3.0K
Commitment is the process whereby stem cells:
3.0K
Hematopoiesis
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
Production 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
Overview 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
Disorders of Leukocytes
982
Leukocyte disorders can lead to either leukopenia, characterized by an abnormally low leukocyte count, or leukocytosis, marked by a very high leukocyte number.
Leukopenia may result from bone marrow disorders, autoimmune diseases, and infectious diseases. For example, conditions such as multiple myeloma and aplastic anemia can impair the bone marrow's ability to produce adequate leukocytes. Similarly, autoimmune diseases like lupus and viral infections such as HIV can prompt the immune...
Leukopenia may result from bone marrow disorders, autoimmune diseases, and infectious diseases. For example, conditions such as multiple myeloma and aplastic anemia can impair the bone marrow's ability to produce adequate leukocytes. Similarly, autoimmune diseases like lupus and viral infections such as HIV can prompt the immune...
982
Multipotency 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


