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

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

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

机译：转录因子TCF-1强制对先天淋巴细胞谱系的承诺

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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.

机译：先天淋巴细胞（ILCS）在免疫和组织稳态中起重要功能，但他们的发展很难理解。通过使用单细胞方法，我们检查了ILC祖细胞的转录和功能异质性，并研究了链接鉴定的子集的前体 - 产品关系。该分析确定了T细胞因子1阳性（TCF-1（+））早期先天淋巴祖细胞（EILPS）中的两个连续阶段，我们将其命名为“指定的EILPS”和“犯罪eilps”。指定的eILPS生成的树突细胞，而犯罪eILPS则大大降低。 TCF-1可分配用于产生指定的EILPS，而是需要产生犯罪eilps所需的。 TCF-1使用了在上游淋巴前体中建立的预先存在的监管景观，以在EILPS中结合染色质。我们的结果提供了对TCF-1促进ILC前体的发育进展的机制的洞察力，同时限制了其树突细胞谱系潜力和对ILC命运的致力于承诺。

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《Nature immunology》 |2019年第9期|共16页
作者
Harly Christelle; Kenney Devin; Ren Gang; Lai Binbin; Raabe Tobias; Yang Qi; Cam Margaret C.; Xue Hai-Hui; Zhao Keji; Bhandoola Avinash;
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作者单位

NCI Lab Genome Integr Ctr Canc Res NIH Bethesda MD 20892 USA;

NCI Lab Genome Integr Ctr Canc Res NIH Bethesda MD 20892 USA;

NHLBI Syst Biol Ctr NIH Bldg 10 Bethesda MD 20892 USA;

NHLBI Syst Biol Ctr NIH Bldg 10 Bethesda MD 20892 USA;

Univ Penn Dept Med Div Translat Med &

Human Genet Perelman Sch Med Philadelphia PA 19104 USA;

Albany Med Coll Dept Immunol &

Microbial Dis Albany NY 12208 USA;

NCI Off Sci &

Technol Resources Off Director Ctr Canc Res NIH Bethesda MD 20892 USA;

Univ Iowa Carver Coll Med Dept Microbiol Interdisciplinary Immunol Grad Program Iowa City IA;

NHLBI Syst Biol Ctr NIH Bldg 10 Bethesda MD 20892 USA;

NCI Lab Genome Integr Ctr Canc Res NIH Bethesda MD 20892 USA;

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正文语种 eng
中图分类医学免疫学;
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1. The transcription factor TCF-1 enforces commitment to the innate lymphoid cell lineage [J] . Harly Christelle, Kenney Devin, Ren Gang, Nature immunology . 2019,第9期

机译：转录因子TCF-1强制对先天淋巴细胞谱系的承诺
2. Group 3 innate lymphoid cells continuously require the transcription factor GATA-3 after commitment (vol 17, pg 169, 2016) [J] . Zhong Chao, Cui Kairong, Wilhelm Christoph, Nature immunology . 2016,第4期

机译：第3组先天淋巴样细胞在承诺后持续需要转录因子GATA-3（第17卷，第169页，2016年）
3. Group 3 innate lymphoid cells continuously require the transcription factor GATA-3 after commitment (vol 17, pg 169, 2016) [J] . Nature immunology . 2016,第2期

机译：第3组先天淋巴样细胞在承诺后持续需要转录因子GATA-3（第17卷，第169页，2016年）
4. Stochastic secretion response to transient stimulus of group-2 innate lymphoid cells (ILC2) [C] . Kazuki Yoda, Kaede Miyata, Nobutake Suzuki, International Symposium on Micro-NanoMechatronics and Human Science . 2017

机译：对第2组先天性淋巴样细胞（ILC2）瞬时刺激的随机分泌反应
5. Transcriptional Landscapes in Lymphocyte Development and Differentiation: TCF-1 Enforces Epigenetic Identity in Developing T Cells and T-BET Resolves Functionally Distinct Memory B Cells [D] . ?Johnson, John L. 2020

机译：淋巴细胞发育和分化中的转录景观：TCF-1在开发T细胞中实施表观遗传鉴定和T-BET解决功能上明显的内存B细胞
6. Group 3 innate lymphoid cells continuously require the transcription factor GATA3 after commitment [O] . Chao Zhong, Kairong Cui, Christoph Wilhelm, -1

机译：第3组先天性淋巴样细胞承诺后连续需要转录因子GATA3
7. Loss of Expression of the WNT/β-Catenin-Signaling Pathway Transcription Factors Lymphoid Enhancer Factor-1 (LEF-1) and T Cell Factor-1 (TCF-1) in a Subset of Peripheral T Cell Lymphomas [O] . David M. Dorfman, Harvey A. Greisman, Aliakbar Shahsafaei 2003

机译：WNT /β-连环蛋白 - 信号通路转录因子淋巴增强剂因子-1（LEF-1）和T细胞因子-1（TCF-1）的表达丧失在外周T细胞淋巴瘤的子集中

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

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