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Transcription factor TCF-1 regulates the functions but not the development of lymphoid tissue inducer subsets in different tissues [Chic-seq]

ABSTRACT: Lymphoid tissue inducer (LTi) cells, known to be critical for the generation of secondary lymphoid tissues, are the founding member of innate lymphoid cells (ILCs). However, how the development and functions of this ILC subset are regulated is far from clear. In this study, we discovered a striking role of the transcription factor TCF-1 in the development of Peyer’s patches (PPs) but not lymph nodes (LNs). Despite TCF-1 is critical for ILC development at multiple stages, we found normal development of LTi cells in TCF-1-deficient mice indicating that dysfunction of these LTi cells led to the deficiency in Peyer’s patches formation. Through bulk and single cell RNA-Seq, we found differential gene expression patterns between LTi cells from the PPs, LNs and the small intestine laminal propria (siLP), and an important role of TCF-1 in regulating the expression of lymphotoxin (LT) specifically in PP LTi cells. Mechanistically, TCF-1 may regulate Lta indirectly through promoting the expression of GATA3, a critical transcription factor in regulating LTi functions. LTβR agonist injection during the embryonic stage partially rescued the formation of PPs in the TCF-1-deficient mice. Thus, a dose effect of LT expression in LTi cells regulated by TCF-1 contributes to a differential regulation of organogenesis of distinct secondary lymphoid structures.

ORGANISM(S): Mus musculus

PROVIDER: GSE190301 | GEO | 2023/08/22

REPOSITORIES: GEO

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Transcription factor TCF-1 regulates the functions but not the development of lymphoid tissue inducer subsets in different tissues [single-cell RNA-seq]

Project description:Lymphoid tissue inducer (LTi) cells, known to be critical for the generation of secondary lymphoid tissues, are the founding member of innate lymphoid cells (ILCs). However, how the development and functions of this ILC subset are regulated is far from clear. In this study, we discovered a striking role of the transcription factor TCF-1 in the development of Peyer’s patches (PPs) but not lymph nodes (LNs). Despite TCF-1 is critical for ILC development at multiple stages, we found normal development of LTi cells in TCF-1-deficient mice indicating that dysfunction of these LTi cells led to the deficiency in Peyer’s patches formation. Through bulk and single cell RNA-Seq, we found differential gene expression patterns between LTi cells from the PPs, LNs and the small intestine laminal propria (siLP), and an important role of TCF-1 in regulating the expression of lymphotoxin (LT) specifically in PP LTi cells. Mechanistically, TCF-1 may regulate Lta indirectly through promoting the expression of GATA3, a critical transcription factor in regulating LTi functions. LTβR agonist injection during the embryonic stage partially rescued the formation of PPs in the TCF-1-deficient mice. Thus, a dose effect of LT expression in LTi cells regulated by TCF-1 contributes to a differential regulation of organogenesis of distinct secondary lymphoid structures.

2023-08-22 | GSE192825 | GEO

Transcription factor TCF-1 regulates the functions but not the development of lymphoid tissue inducer subsets in different tissues [DNase-seq]

2023-08-22 | GSE190300 | GEO

Transcription factor TCF-1 regulates the functions but not the development of lymphoid tissue inducer subsets in different tissues [RNA-seq]

2023-08-22 | GSE190299 | GEO

Differential Expression of the Transcription Factor GATA3 Specifies Lineage and Functions of Innate Lymphoid Cells

Project description:Lymphoid tissue inducer (LTi) cells are regarded as a subset of innate lymphoid cells (ILCs). However, these cells are not derived from the ILC common progenitor, which generates other ILC subsets and is defined by the expression of the transcription factor PLZF. Here we examined transcription factor(s) determining the fate of LTi progenitor versus non-LTi ILC progenitor. Conditional deletion of Gata3 resulted in the loss of PLZF+ non-LTi progenitors but not the LTi progenitors that expressed the transcription factor RORγt. Consistently, PLZF+ non-LTi progenitors expressed high amounts of GATA3 whereas GATA3 expression was low in RORγt+ LTi progenitors. The generation of both progenitors required the transcriptional regulator Id2, which defines the common helper-like innate lymphoid progenitor, but not cytokine signaling. Nevertheless, low GATA3 expression was necessary for the generation of functionally mature LTi cells. Thus, differential expression of GATA3 determines the fates and functions of distinct ILC progenitors.

2019-12-24 | GSE93863 | GEO

Single cell analysis defines the divergence between the innate lymphoid cell and lymphoid tissue inducer lineages

Project description:The precise lineage relationships between innate lymphoid cells (ILC) and the lymphoid tissue inducer (LTi) are poorly understood. Using single-cell multiplex transcriptional analysis of 100 lymphoid genes and single-cell cultures of fetal liver precursor cells, we identified the common proximal precursor to these lineages and showed that its bifurcation was precisely marked by the differential induction of the transcription factors PLZF and TCF1. Acquisition of individual ILC1/2/3-specific effector programs was initiated later, at the common ILC precursor (ILCP) stage, by transient expression of mixed ILC1/2/3 transcriptional patterns whereas, in contrast, LTi development did not go through multilineage priming. These findings provide novel insights into divergent mechanisms of ILC and LTi lineage differentiation and establish a high-resolution map of their development.

2015-12-30 | GSE76407 | GEO

Multi-transcription factor reporter mice delineate early precursors to the LTi and ILC lineages

Project description:Transcription factor (TF) reporter mice have proved integral to the characterization of murine innate lymphoid cell (ILC) development and function. Here, we implemented a CRISPR/Cas9-generated combinatorial reporter approach for the simultaneous resolution of several key TFs throughout ILC development in both the fetal liver and adult bone marrow. We demonstrate that the Tcf7-expressing early innate lymphoid progenitor (EILP) and the common helper innate lymphoid progenitor (CHILP) both contain a heterogeneous mixture of committed ILC and Lymphoid Tissue-inducer (LTi) precursors, rather than a shared precursor to these lineages. Moreover, the earliest specified precursor to the LTi lineage was identified upstream of these populations, prior to the expression of Tcf7. These findings match dynamic changes in chromatin accessibility associated with the expression of key TFs (ie. Gata3 and Rorc), highlighting the distinct origins of ILC and LTi lineages at the epigenetic and functional levels, and provide a revised map for ILC development.

2020-09-28 | GSE150763 | GEO

Gene expression analysis of CD4+ and CD4- ILC1 subsets by RNAseq

Project description:Innate lymphoid cell (ILC) subsets that mirror helper T cells in their effector cytokine profiles have recently emerged as central players in both homeostatic and inflammatory conditions. Like their Th1, Th2 and Th17/Th22 helper T cell counterparts, ILC subsets are categorized based on their expression of specific transcription factors and effector cytokines: group 1 ILC (ILC1) express T-bet and IFN-Î³; group 2 ILC (ILC2) express GATA-3 and type 2 effector cytokines such as IL-13 and IL-5; and group 3 ILC (ILC3) express RORgt and the cytokines IL-22 and/or IL-17. Under this nomenclature, natural killer (NK) cells and lymphoid tissue inducers (LTi) are considered ILC1 and ILC3, respectively. ILC1 contain both CD4+ and CD4- populations, but whether this phenotypic characteristic reflects functional differences between these two populations is unknown. These studies examine the gene expression profiles of CD4+ vs CD4- ILC1 in a cohort of healthy control subjects. ILC subsets were isolated from the peripheral blood of healthy control subjects. cDNA was isolated and amplified from sorted populations, and gene expression was analyzed by RNAseq

2015-12-31 | E-GEOD-69596 | biostudies-arrayexpress

Expression data from small intestinal Lin-c-Kit+Sca-1- cells and Lin-c-Kit-Sca-1- cells.

Project description:Small intestinal innate lymphoid cells (ILCs) are known to regulate intestinal epithelial cell homeostasis and to help prevent pathogenic bacterial infections, by producing IL-22. However, other functions of these cells and the lineal relationship between ILCs and lymphoid or myeloid cells have not been clear. We performed a global gene expression analysis to examine which genes are highly expressed by small intestinal ILCs (Lin-c-Kit+Sca-1- cells) compared with non-ILCs (Lin-c-Kit-Sca-1- cells). To examine the gene expression profiles of ILCs within the small intestinal lamina propria (LP), we isolated Lingeage (Lin)-c-Kit+Sca-1- cells [consisting of NKp46+ ILC22 (Lin-c-Kit+Sca-1-NKp46+ cells) and LTi-like ILC (Lin-c-Kit+Sca-1-CD4+ cells)] as the ILC population, and Lin-c-Kit-Sca-1- cells as the non-ILC population, from the small intestinal LP of 8 week-old mice by FACS, then compared the gene expression profiles between these two populations by microarray analysis.

2012-09-15 | E-GEOD-40882 | biostudies-arrayexpress

Bcl6 is a subset defining transcription factor of Lymphoid Tissue inducer-like ILC3

Project description:Innate lymphoid cells (ILC) are tissue-resident effector cells with important roles in tissue homeostasis, protective immunity and inflammatory disease. Current nomenclature divides ILC into subsets based on the expression of master transcription factors and effector cytokine programs. In mucosal barrier tissues, group 3 ILC (ILC3) have been defined by the expression of the master transcription factor RORgt. However, ILC3 can be further subdivided into two major subsets – natural cytotoxicity receptor-expressing (NCR+) ILC3 and lymphoid tissue inducer (LTi)-like ILC3 which share type 3 effector modules but also exhibit significant ontological, transcriptional, phenotypic and functional heterogeneity. In particular, LTi-like ILC3 exhibit effector functions not typically associated with other RORgt-expressing lymphocytes, provoking the hypothesis that other master transcription factors may contribute to LTi-like ILC3 biology. Here we identify Bcl6 as an LTi-like ILC3 associated transcription factor in both mice and humans. Deletion of Bcl6 led to dysregulation of the LTi-like ILC3 transcriptional program and changes to subset-specific phenotypic markers and effector functions. Strikingly, loss of Bcl6 enhanced expression of the type 3 effector cytokines IL-17A and IL-17F in LTi-like ILC3, which was found to be in part dependent upon the commensal microbiota. Together these findings implicate Bcl6 as an ILC3 subset-defining transcription factor and part of a network that confers phenotype and function on LTi-like ILC3. Our study further provides a missing link to redefine analogous immune modules in innate and adaptive lymphocyte responses.

2023-10-31 | GSE228852 | GEO

Distinct waves from the hemogenic endothelium give rise to layered Lymphoid Tissue Inducer cell ontogeny [bulk RNA-seq]

Project description:LTi cells are part of the ILC family and essential for the formation of secondary lymph nodes within the embryo. This data set contains the analysis of lymphoid tissue (LTi) cell ontogeny, studied by expression profile analysis with RNA bulk sequencing of the populations associated with LTi ontogeny isolated from fetal liver vs. embryonic periphery at embryonic stage E13.5. They indicate a proliferating precursor population mainly in the fetal liver, while the embryonic periphery harbors the definitive lineage.

2020-08-01 | GSE153607 | GEO

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