The Transcription Factor ThPOK Regulates ILC3 Lineage Homeostasis and Function during Intestinal Infection II
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PROVIDER: PRJNA841977 | ENA |
REPOSITORIES: ENA
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Project description:To investigate the role of ThPOK in the regulation of ILC3 development and function, we established conventional ThPOK knockout mice and carried out single-cell RNA sequencing (BD Rhapsody) on intestinal ILC3s.
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Project description:To investigate the role of ThPOK in the regulation of ILC3 development and function, we established conventional ThPOK knockout mice.
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Project description:The Transcription Factor ThPOK Regulates ILC3 Lineage Homeostasis and Function during Intestinal Infection
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Project description:PD-1 is constitutively expressed on a fraction of ILC3 in the gut. To identify the transcriptional differences between PD1+ and PD1- ILC3, we have sorted these subsets and analysed their transcriptional regulation by RNA-Seq.
2024-02-29 | GSE254794 | GEO
Project description:Group 3 innate lymphoid cells (ILC3) are major regulators of inflammation, infection, microbiota composition and metabolism. ILC3 and neuronal cells were shown to interact at discrete mucosal locations to steer mucosal defence. Nevertheless, whether neuroimmune circuits operate at an organismal level, integrating extrinsic environmental signals to orchestrate ILC3 responses remains elusive. Here we show that light-entrained and brain-tuned circadian circuits regulate enteric ILC3, intestinal homeostasis and the host lipid metabolism. We found that enteric ILC3 display circadian expression of clock genes and ILC3-related transcription factors. ILC3-autonomous ablation of the circadian regulator Arntl led to disrupted gut ILC3 homeostasis, impaired epithelial reactivity, deregulated microbiome, increased susceptibility to bowel infection and disrupted lipid metabolism. Loss of ILC3-intrinsic Arntl shaped the gut postcode receptors of ILC3. Strikingly, light-dark cycles, feeding rhythms and microbial cues differentially regulated ILC3 clocks, with light signals as major entraining cues of ILC3. Accordingly, surgical- and genetically-induced deregulation of brain rhythmicity led to disrupted circadian ILC3 oscillations, deregulated microbiome and altered lipid metabolism. Our work reveals a circadian circuitry that translates environmental light cues into enteric ILC3, shaping intestinal health and organismal homeostasis.
2019-08-02 | GSE135235 | GEO
Project description:Although BTB-zinc finger (BTB-ZF) transcription factors control the differentiation of multiple hematopoietic and immune lineages, how they function is poorly understood. The BTB-ZF factor Thpok controls intrathymic CD4+ T cell development and expression of most CD4+- and CD8+-lineage genes. Here, we identify the nucleosome remodeling and deacetylase (NuRD) complex as a novel Thpok cofactor. We locate three amino-acid residues within the Thpok BTB domain that are required for both NuRD binding and Thpok functions, and show that NuRD recruitment recapitulates the functions of the Thpok BTB domain. NuRD mediates Thpok repression of CD8+-lineage genes, including the transcription factor Runx3, but is dispensable for Cd4 expression. We show that these functions cannot be performed by the BTB domain of the Thpok-related factor Bcl6, which fails to bind NuRD. Thus, cofactor binding critically contributes to the functional specificity of BTB-zinc finger factors, which control the differentiation of most hematopoietic subsets.
2022-06-10 | GSE199739 | GEO
Project description:The transcription factor ThPOK (encoded by Zbtb7b) is well known for its role as a master regulator of CD4 lineage commitment in the thymus. Here, we report a novel role for ThPOK as a critical and multifaceted regulator of myeloid lineage commitment, differentiation and maturation. Using reporter and knockout mouse models combined with CITE-Seq, Smart-Seq2, progenitor transfer and clonogenic assays and we show that ThPOK controls monocyte-DC versus granulocyte lineage production during homeostatic differentiation, and serves as a brake for neutrophil maturation in granulocyte lineage-specified cells through transcriptional regulation of lineage-specific transcription factors and RNA via altered mRNA splicing to reprogram intron retention.
2023-06-05 | GSE163843 | GEO
Project description:The transcription factor ThPOK (encoded by Zbtb7b) is well known for its role as a master regulator of CD4 lineage commitment in the thymus. Here, we report a novel role for ThPOK as a critical and multifaceted regulator of myeloid lineage commitment, differentiation and maturation. Using reporter and knockout mouse models combined with CITE-Seq, Smart-Seq2, progenitor transfer and clonogenic assays and we show that ThPOK controls monocyte-DC versus granulocyte lineage production during homeostatic differentiation, and serves as a brake for neutrophil maturation in granulocyte lineage-specified cells through transcriptional regulation of lineage-specific transcription factors and RNA via altered mRNA splicing to reprogram intron retention.
2023-06-05 | GSE163837 | GEO
Project description:The transcription factor Thpok is essential for CD4 T cell development in the thymus and remains expressed in post-thymic CD4 T cells. We post-thymically inactivated Thpok and compared microarray gene expression in Thpok-deficient CD4 T cells to that in their wildtype CD4 or CD8 counterparts We show that Thpok constrains the transcriptional circuitry to maintain CD4+-lineage integrity in naM-CM-/ve cells and to couple effector differentiation to environmental cues after antigenic stimulation. Redundantly with the related factor LRF, Thpok is continuously needed to prevent the trans-differentiation of mature CD4+ into -CD8+ T cells. We activated naM-CM-/ve CD4 T cells (either wild-type or Thpok-deficient) and CD8 T cells (wild-type) in vitro under Th1 conditions. Differentiated effectors were sorted 4 days after activation into CD4+CD8- and CD4-CD8+ (wild-type) and CD4+CD8- and CD4+CD8+ (Thpok-deficient) subsets. Total RNA was extracted from sorted subsets and processed for microarray analyses (Affymetrix Mouse Exon 1.0 ST array) at the NCI microarray facility, following the manufacturerM-bM-^@M-^Ys recommendation. Data is from 3 replicates (except wild-type CD4-CD8+ cells, for which two samples only were processed), generated from two distinct cell preparations.
2014-08-15 | E-GEOD-57846 | biostudies-arrayexpress
Project description:Group 3 innate lymphoid cells (ILC3) are innate immune effectors that contribute to host defense. Whether ILC3 functions are stably modified following pathogen encounter is unknown. Here we assess the impact of a time-restricted enterobacterial challenge to long-term ILC3 activation. We found that intestinal ILC3 persist for months in an activated state following exposure to Citrobacter rodentium. Upon rechallenge, these “trained” ILC3 proliferate, display enhanced interleukin (IL)-22 responses, and have a superior cell-intrinsic capacity to control infection compared to naïve ILC3. Metabolic changes occur in C. rodentium-exposed ILC3 but only trained ILC3 have enhanced proliferative capacity that contributes to elevated IL-22 production. Accordingly, a limited encounter with a pathogen can promote durable phenotypic and functional changes in intestinal ILC3 that contribute to long-term mucosal defense.
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