对B-淋巴细胞系的承诺取决于转录因子Pax5的转录因子
S L Nutt1, B Heavey, A G Rolink
1Research Institute of Molecular Pathology, Vienna, Austria.
Nature
|October 19, 1999
概括
帕克斯5基因对B细胞发育至关重要. 缺少Pax5,亲B细胞可以转化为其他类型的血液细胞,突出Pax5在B血统承诺中的作用.
科学领域:
- 免疫学 免疫学 免疫学
- 发展生物学 发展生物学
- 遗传学 是一个遗传学.
背景情况:
- 帕克斯5基因编码B细胞特异激活蛋白 (BSAP).
- 在体内,Pax5对于B淋巴细胞谱系在超越亲B细胞阶段的进展至关重要.
- 在特定条件下,Pro-B细胞可以在没有Pax5的情况下在体外繁殖.
研究的目的:
- 为了研究Pax5在体外B细胞分化中的作用.
- 为了确定Pax5缺乏的亲B细胞是否受到血统限制.
- 了解Pax5如何影响血统承诺和基因表达.
主要方法:
- 在体外培养Pax5-缺乏的 (Pax5-/-) 亲B细胞.
- 通过逆转录病毒转导恢复Pax5表达.
- 用细胞因子刺激Pax5-/-亲B细胞以评估分化潜力.
- 分析Pax5恢复和没有Pax5恢复的Pax5-/-亲B细胞中的基因表达特征.
主要成果:
- 在体外,Pax5-/- 亲B细胞未能分化为B细胞,除非重新引入Pax5.
- 帕克斯5-/- 亲B细胞表现出多能性,分化为巨细胞,骨质细胞,树突细胞,粒细胞和自然杀手细胞.
- 帕克斯5-/- 亲B细胞表现出来自各种造血系的基因的杂乱转录.
- 恢复Pax5活性抑制了血统不适当的基因表达.
结论:
- 在体外,Pax5对于B细胞与亲B细胞的分化是不可或缺的.
- 帕克斯5的功能是抑制替代血统命运,从而强制执行B血统承诺.
- 帕克斯5通过限制谱系潜力,作为造血干细胞分化的关键调节者.
相关概念视频
Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
Master Transcription Regulators
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...
Lineage Commitment
Commitment is the process whereby stem cells:
General Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
Master Transcription Regulators
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...


