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一个定时的表观遗传开关平衡了胸腺中的T和ILC血统比例

Nicholas A Pease^1,2, Kathryn M Denecke¹, Lihua Chen¹

¹Department of Bioengineering, University of Washington, Seattle, WA 98105, USA.

Development (Cambridge, England)

|December 10, 2024

概括

表观遗传开关控制细胞发育时间. 延迟 Bcl11b 基因激活在原始细胞中会减少 T 细胞数量,但通过重定向细胞命运来增强先天性淋巴细胞 (ILC) 的产生.

科学领域:

发育生物学是发展生物学.
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
细胞命运的决定细胞命运的决定

背景情况:

多能原始细胞产生各种各样的细胞类型.
表观遗传开关可以延迟基因激活,从而影响细胞谱系的决定.
Bcl11b是T细胞承诺的关键转录因子,在延迟后被激活.

研究的目的:

研究延迟Bcl11b激活在控制细胞谱系决策中的作用.
分析修改Bcl11b增强剂如何影响T细胞和先天性淋巴细胞 (ILC) 生产.
了解由于基因激活时间改变而导致细胞命运重定向的机制基础.

主要方法:

对被删除的远端Bcl11b增强剂的老鼠祖先的分析.
在甲状腺中量化T细胞和ILC输出.
在祖先种群中评估转录因子表达,包括PLZF.

主要成果:

删除Bcl11b增强剂将基因激活延迟延长了大约3天.
延迟的Bcl11b激活减少了T细胞的产生.
延迟的Bcl11b激活通过重定向未被激活的祖先来增加ILC生成.
在Bcl11b延迟时观察到PLZF的升级,这是ILC特异性因素.
尽管PLZF上调,但Bcl11b表达仍然是2型ILC分化所需的.

结论:

控制基因激活时间的表观遗传开关对于调节细胞类型输出至关重要.
基因激活的时间和顺序可以通过表观遗传学来调节,以控制细胞比例.
延迟的Bcl11b激活将祖先命运重定向到ILCs,突出了早期淋巴细胞发育的可塑性.

关键词:

在 Bcl11bb 中.发展时间表的发展时间表.表观遗传的开关是表观遗传的开关.基因监管网络是基因监管网络.天生的淋巴细胞是先天性淋巴细胞.鼠标鼠标是一个鼠标.在PLZF中.在T细胞,T细胞.

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