当前位置:科学网首页 > 小柯机器人 >详情
Irf8剂量依赖性调控谱系选择机制
作者:小柯机器人 发布时间:2021/2/20 11:01:49

日本横滨市立大学医学系研究科Tomohiko Tamura和Akira Nishiyama研究组合作取得最新进展。他们揭示RUNX–CBFβ驱动的增强子指导树突状细胞(DC)和单核细胞之间Irf8剂量依赖性谱系选择。这一研究成果发表在2021年2月18日出版的国际学术期刊《自然-免疫学》上。

他们确定了由Irx8转录起始位点下游的RUNX–CBFβ驱动的增强子56kb。体内该增强子的缺失显著降低了从祖细胞阶段开始贯穿整个髓系的Irf8表达,从而导致普通DC祖细胞的丧失和Ly6C +单核细胞的过度生产。他们证明,造血祖细胞中IRF8的高、低或空表达分别通过与其他转录因子协同作用的不同组增强子的表观遗传学调节,分别促进向1型常规DC,Ly6C +单核细胞或中性粒细胞的分化。他们的结果说明了IRF8在髓样细胞系统内以剂量依赖性方式控制谱系选择的机制。

研究人员表示,转录因子IRF8对于单核细胞和DC的发育至关重要,而它抑制嗜中性细胞的分化。目前尚不清楚Irf8的表达如何受到调控,以及该单一转录因子如何支持单核细胞和DC的生成。

附:英文原文

Title: A RUNX–CBFβ-driven enhancer directs the Irf8 dose-dependent lineage choice between DCs and monocytes

Author: Koichi Murakami, Haruka Sasaki, Akira Nishiyama, Daisuke Kurotaki, Wataru Kawase, Tatsuma Ban, Jun Nakabayashi, Satoko Kanzaki, Yoichi Sekita, Hideaki Nakajima, Keiko Ozato, Tohru Kimura, Tomohiko Tamura

Issue&Volume: 2021-02-18

Abstract: The transcription factor IRF8 is essential for the development of monocytes and dendritic cells (DCs), whereas it inhibits neutrophilic differentiation. It is unclear how Irf8 expression is regulated and how this single transcription factor supports the generation of both monocytes and DCs. Here, we identified a RUNX–CBFβ-driven enhancer 56kb downstream of the Irf8 transcription start site. Deletion of this enhancer in vivo significantly decreased Irf8 expression throughout the myeloid lineage from the progenitor stages, thus resulting in loss of common DC progenitors and overproduction of Ly6C+ monocytes. We demonstrated that high, low or null expression of IRF8 in hematopoietic progenitor cells promotes differentiation toward type 1 conventional DCs, Ly6C+ monocytes or neutrophils, respectively, via epigenetic regulation of distinct sets of enhancers in cooperation with other transcription factors. Our results illustrate the mechanism through which IRF8 controls the lineage choice in a dose-dependent manner within the myeloid cell system.

DOI: 10.1038/s41590-021-00871-y

Source: https://www.nature.com/articles/s41590-021-00871-y

期刊信息

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