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转录因子Hhex与共抑制因子Tle3协同促进记忆B细胞发育
2020-06-30 21:27

美国加州大学旧金山分校Jason G. Cyster研究团队发现,转录因子Hhex与共抑制因子Tle3协同促进记忆B细胞发育。该项研究成果于2020年6月29日在线发表在《自然—免疫学》上。

通过单细胞RNA测序分析,研究人员鉴定了分化为记忆B细胞(MBC)过程中的生发中心(GC)B细胞群体。使用一种可诱导的CRISPR–Cas9筛选方法,研究人员确定了造血表达的同源盒蛋白Hhex是调节MBC分化的转录因子。在筛选中还发现了共抑制因子Tle3,并且发现它与Hhex相互作用以促进MBC的发育。Bcl-6直接抑制GC B细胞中的Hhex。
 
相反,缺乏Hhex的MBC表现出Bcl6表达的增加和Bcl-6靶基因Bcl2表达的降低。Bcl-2的过表达能够挽救Hhex缺陷细胞中的MBC分化。研究人员还确定了Ski是参与MBC分化的Hhex诱导型转录因子。这些发现表明,Hhex–Tle3在调控MBC分化的转录途径中发挥了重要作用。
 
据悉,MBC对于长期的体液免疫至关重要。但是,涉及MBC分化的转录因子仍不清楚。
 
附:英文原文

Title: The transcription factor Hhex cooperates with the corepressor Tle3 to promote memory B cell development

Author: Brian J. Laidlaw, Lihui Duan, Ying Xu, Sara E. Vazquez, Jason G. Cyster

Issue&Volume: 2020-06-29

Abstract: Memory B cells (MBCs) are essential for long-lived humoral immunity. However, the transcription factors involved in MBC differentiation are poorly defined. Here, using single-cell RNA sequencing analysis, we identified a population of germinal center (GC) B cells in the process of differentiating into MBCs. Using an inducible CRISPR–Cas9 screening approach, we identified the hematopoietically expressed homeobox protein Hhex as a transcription factor regulating MBC differentiation. The corepressor Tle3 was also identified in the screen and was found to interact with Hhex to promote MBC development. Bcl-6 directly repressed Hhex in GC B cells. Reciprocally, Hhex-deficient MBCs exhibited increased Bcl6 expression and reduced expression of the Bcl-6 target gene Bcl2. Overexpression of Bcl-2 was able to rescue MBC differentiation in Hhex-deficient cells. We also identified Ski as an Hhex-induced transcription factor involved in MBC differentiation. These findings establish an important role for Hhex–Tle3 in regulating the transcriptional circuitry governing MBC differentiation.

DOI: 10.1038/s41590-020-0713-6

Source: https://www.nature.com/articles/s41590-020-0713-6

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex


本期文章:《自然—免疫学》:Online/在线发表

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