Baf155通过染色质原始化控制了造血细胞的分化和再生
Jun Wu1, Changxu Fan2, Ashraf Ul Kabir1
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cell reports
|August 1, 2024
概括
Baf155对于造血干细胞的功能至关重要. 它的缺失会损害血细胞再生和免疫反应,突出显示它在染色质原始化中对血液发育的作用.
科学领域:
- 血液学 血液学 血液学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 染色素原始化对于细胞分化和发育至关重要.
- 控制染色素原始化的精确机制仍然不完全理解.
- BAF染色体重塑复合体在基因调节中起着至关重要的作用.
研究的目的:
- 阐明Baf155亚单元在血液造血干细胞和原生细胞 (HSPC) 中的染色素原始化中的作用.
- 研究Baf155缺乏对造血细胞再生和免疫功能的功能后果.
- 了解Baf155在血统承诺中的功能背后的分子机制.
主要方法:
- 使用了一种缺乏HSPC中Baf155亚单元的小鼠模型.
- 进行了移植和5-甲 (5-FU) 损伤模型,以评估造血再生.
- 进行了单核多组学分析,以检查染色质可访问性和基因调节.
主要成果:
- 缺乏Baf155的HSPC显著减少成熟血细胞的产生,包括中性粒细胞,B细胞和CD8+T细胞.
- 在移植和5-FU损伤后,Baf155的损失导致了受损的造血再生.
- Baf155缺乏导致关键调节区域无法建立可访问的染色质,影响了谱系转录因子的结合.
- 瘤生长在缺乏Baf155的模型中得到了增强,这表明了免疫抑制瘤微环境.
结论:
- Baf155是染色质原始化的关键调节者,用于造血系的发育.
- 缺少Baf155严重影响了造血细胞的再生,并改变了免疫细胞的稳定性.
- Baf155的失调会影响染色体的可访问性,导致血统分化受损,并导致免疫抑制性瘤微环境.
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
01:21Lineage Commitment
3.0K
Commitment is the process whereby stem cells:
3.0K
01:14Maintenance of the ES Cell State
2.2K
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...
2.2K
01:32Chromatin Modification in iPS Cells
1.6K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.6K
02:23Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
01:24Methods of Nuclear Reprogramming
1.8K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
1.8K