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TCF-1调控先天淋巴细胞命运谱系的确立
作者:小柯机器人 发布时间:2019/9/2 15:01:00

美国国立卫生研究院Avinash Bhandoola团队近期发现转录因子TCF-1调控先天淋巴细胞(ILC)命运谱系的确立。该项研究成果发表在2019年9月出版的《自然—免疫学》上。

通过使用单细胞测序技术,研究人员分析了先天淋巴细胞(ILC)前体细胞的转录和功能异质性,并研究了连接所鉴定亚群中前体细胞与分化细胞的关系。该分析确定了T细胞因子1阳性(TCF-1+)早期先天淋巴前体细胞(EILP)中ILC发展的两个连续阶段,研究人员将其命名为“分化EILP”和“定型EILP”。分化EILP能够产生树突细胞,而这种潜力在定型EILP中大大降低。TCF-1对于产生分化EILP是不必要的,但是对于产生定型EILP是需要的。TCF-1利用已预先存在的调节性表观状态(由分化上游的淋巴前体细胞所建立)来结合EILP中的染色质。

这些研究结果对TCF-1促进ILC前体细胞发育进程、并同时限制它们的树突细胞谱系分化潜力并对ILC命运进行确定的机制提供了见解。

据悉,先天淋巴细胞(ILC)在免疫和组织稳态中发挥重要作用,但其发育过程尚不清楚。

附:英文原文

Title: The transcription factor TCF-1 enforces commitment to the innate lymphoid cell lineage

Author: Christelle Harly, Devin Kenney, Gang Ren, Binbin Lai, Tobias Raabe, Qi Yang, Margaret C. Cam, Hai-Hui Xue, Keji Zhao, Avinash Bhandoola

Issue&Volume: Volume 20 Issue 9

Abstract: Innate lymphoid cells (ILCs) play important functions in immunity and tissue homeostasis, but their development is poorly understood. Through the use of single-cell approaches, we examined the transcriptional and functional heterogeneity of ILC progenitors, and studied the precursor–product relationships that link the subsets identified. This analysis identified two successive stages of ILC development within T cell factor 1-positive (TCF-1+) early innate lymphoid progenitors (EILPs), which we named ‘specified EILPs’ and ‘committed EILPs’. Specified EILPs generated dendritic cells, whereas this potential was greatly decreased in committed EILPs. TCF-1 was dispensable for the generation of specified EILPs, but required for the generation of committed EILPs. TCF-1 used a pre-existing regulatory landscape established in upstream lymphoid precursors to bind chromatin in EILPs. Our results provide insight into the mechanisms by which TCF-1 promotes developmental progression of ILC precursors, while constraining their dendritic cell lineage potential and enforcing commitment to ILC fate.

DOI: 10.1038/s41590-019-0445-7

Source: https://www.nature.com/articles/s41590-019-0445-7

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