ILC progenitor CEL-seq
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE75851 | GEO | 2016/10/04
SECONDARY ACCESSION(S): PRJNA305531
REPOSITORIES: GEO
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Project description:ILC2 contribute to immune homeostasis, protective immunity and tissue repair. However, an understanding of the microenvironmental factors and transcriptional circuits that support development of these innate lymphocytes within lymphoid organs, alongside their adaptive T and B cell relatives, is only starting to emerge. Here we demonstrate that functional ILC2 arise in the embryonic thymus, from shared T cell precursors, and precede the emergence of CD4+CD8+ (double-positive) T cells. Strikingly, RORa expression repressed T cell development, whilst promoting ILC2 in the thymus. Thymic ILC2 go on to contribute to the innate type-2 response at mucosal tissues with preferential colonisation of the intestinal lamina propria. From RNAseq, ATACseq and ChIPseq data we propose a revised transcriptional circuit to explain the enigmatic co-development of T cells, ILC2 and NK cells from common progenitors in the thymus. When Notch signalling is present, Bcl11b dampens Nfil3/Id2 expression, permitting E protein-directed T cell commitment. However, concomitant expression of RORa overrides the Nfil3/Id2 repression, allowing Id2 to repress E proteins and promote ILC2 differentiation. Thus, we demonstrate that RORa expression represents a critical checkpoint at the bifurcation of the T cell and ILC2 lineages in the embryonic thymus.
2020-11-03 | GSE146744 | GEO
Project description:ILC2 contribute to immune homeostasis, protective immunity and tissue repair. However, an understanding of the microenvironmental factors and transcriptional circuits that support development of these innate lymphocytes within lymphoid organs, alongside their adaptive T and B cell relatives, is only starting to emerge. Here we demonstrate that functional ILC2 arise in the embryonic thymus, from shared T cell precursors, and precede the emergence of CD4+CD8+ (double-positive) T cells. Strikingly, RORa expression repressed T cell development, whilst promoting ILC2 in the thymus. Thymic ILC2 go on to contribute to the innate type-2 response at mucosal tissues with preferential colonisation of the intestinal lamina propria. From RNAseq, ATACseq and ChIPseq data we propose a revised transcriptional circuit to explain the enigmatic co-development of T cells, ILC2 and NK cells from common progenitors in the thymus. When Notch signalling is present, Bcl11b dampens Nfil3/Id2 expression, permitting E protein-directed T cell commitment. However, concomitant expression of RORa overrides the Nfil3/Id2 repression, allowing Id2 to repress E proteins and promote ILC2 differentiation. Thus, we demonstrate that RORa expression represents a critical checkpoint at the bifurcation of the T cell and ILC2 lineages in the embryonic thymus.
2020-11-03 | GSE146743 | GEO
Project description:ILC2 contribute to immune homeostasis, protective immunity and tissue repair. However, an understanding of the microenvironmental factors and transcriptional circuits that support development of these innate lymphocytes within lymphoid organs, alongside their adaptive T and B cell relatives, is only starting to emerge. Here we demonstrate that functional ILC2 arise in the embryonic thymus, from shared T cell precursors, and precede the emergence of CD4+CD8+ (double-positive) T cells. Strikingly, RORa expression repressed T cell development, whilst promoting ILC2 in the thymus. Thymic ILC2 go on to contribute to the innate type-2 response at mucosal tissues with preferential colonisation of the intestinal lamina propria. From RNAseq, ATACseq and ChIPseq data we propose a revised transcriptional circuit to explain the enigmatic co-development of T cells, ILC2 and NK cells from common progenitors in the thymus. When Notch signalling is present, Bcl11b dampens Nfil3/Id2 expression, permitting E protein-directed T cell commitment. However, concomitant expression of RORa overrides the Nfil3/Id2 repression, allowing Id2 to repress E proteins and promote ILC2 differentiation. Thus, we demonstrate that RORa expression represents a critical checkpoint at the bifurcation of the T cell and ILC2 lineages in the embryonic thymus.
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Project description:ILC2 contribute to immune homeostasis, protective immunity and tissue repair. However, an understanding of the microenvironmental factors and transcriptional circuits that support development of these innate lymphocytes within lymphoid organs, alongside their adaptive T and B cell relatives, is only starting to emerge. Here we demonstrate that functional ILC2 arise in the embryonic thymus, from shared T cell precursors, and precede the emergence of CD4+CD8+ (double-positive) T cells. Strikingly, RORa expression repressed T cell development, whilst promoting ILC2 in the thymus. Thymic ILC2 go on to contribute to the innate type-2 response at mucosal tissues with preferential colonisation of the intestinal lamina propria. From RNAseq, ATACseq and ChIPseq data we propose a revised transcriptional circuit to explain the enigmatic co-development of T cells, ILC2 and NK cells from common progenitors in the thymus. When Notch signalling is present, Bcl11b dampens Nfil3/Id2 expression, permitting E protein-directed T cell commitment. However, concomitant expression of RORa overrides the Nfil3/Id2 repression, allowing Id2 to repress E proteins and promote ILC2 differentiation. Thus, we demonstrate that RORa expression represents a critical checkpoint at the bifurcation of the T cell and ILC2 lineages in the embryonic thymus.
2020-11-03 | GSE146740 | GEO
Project description:Innate lymphoid cells (ILC) are tissue-resident effector cells with important roles in tissue homeostasis, protective immunity and inflammatory disease. Here we investigated the role of the transcription factor Bcl6 in small intestinal innate lymphoid cells. Specifically, we performed single-cell RNA-seq on total small intestine lamina propria ILCs from tamoxifen-treated Id2-CreERT2 ROSA26-tdRFP Bcl6-fl/fl mice and Id2-CreERT2 ROSA26-tdRFP controls.
2023-10-31 | E-MTAB-12864 | biostudies-arrayexpress
Project description:Innate lymphoid cells (ILCs) represent innate versions of T helper and cytotoxic T cells that differentiate from committed ILC precursors (ILCP). Still, how ILCP relate to mature tissue-resident ILCs remains unclear. We identify ILCP that are present in the blood and all tested lymphoid and non-lymphoid human tissues. Human ILCP fail to express the signature transcription factors (TF) and cytokine outputs of mature NK cells and ILCs but are epigenetically poised to do so. Human ILCP robustly generate all ILC subsets in vitro and in vivo. While human ILCP express RAR related orphan receptor C (RORC), circulating ILCP can be found in RORC-deficient patients that retain potential for EOMES+ NK cells, T-BET+ ILC1, GATA-3+ ILC2 and for IL-22+ but not for IL-17A+ ILC3. We propose a model of tissue ILC differentiation (‘ILC-poiesis’) whereby diverse ILC subsets are generated in situ from ILCP in response to environmental stressors, inflammation and infection.
2017-03-19 | GSE90640 | GEO
Project description:Innate lymphoid cells (ILCs) are recently identified lymphocytes that limit infection and promote tissue repair at mucosal surfaces. However, the pathways underlying ILC development remain unclear. Here we show that the transcription factor NFIL3 directs the development of a committed bone marrow precursor that differentiates into all known ILC lineages. NFIL3 was required in the common lymphoid progenitor (CLP), and was essential for the differentiation of CLP, a bone marrow cell population that gives rise to all known ILC lineages. Clonal differentiation studies revealed that CXCR6+ cells within the CLP population differentiate into all ILC lineages but not T- and B-cells. We further show that NFIL3 governs ILC development by directly regulating expression of the transcription factor TOX. These findings establish that NFIL3 directs the differentiation of a committed ILC precursor that gives rise to all ILC lineages and provide insight into the defining role of NFIL3 in ILC development. This experiment is to compare gene expression profiles between wild-type and Nfil3-/- common lymphoid progenitor (CLP) cells to identify genes regulated by NFIL3. There are 6 samples in this experiment, including 3 biological replicates for wild-type CLPs and 3 biological replicates for Nfil3-/- CLPs. All mice used are on the C57BL/6 background.
2014-10-16 | E-GEOD-62337 | biostudies-arrayexpress
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
Project description:Innate lymphoid cells (ILCs) have emerged as essential players in the skin-associated immune system in health and inflammatory skin diseases. Their low numbers and lack of specific markers hampered extensive characterization and consequently resulted in limited knowledge of their protein expression. Here, we combined flow cytometry and state-of-the-art proteomics to comprehensively describe the proteins constitutively expressed by ILC2 and ILC3 subsets derived from healthy human skin and peripheral blood. We quantified 6666 proteins from skin ILC and identified 608 differentially expressed proteins in the investigated subsets. In addition to the current analyses, highlighting new functions of ILC, the ILC proteomic libraries and the proteomes of the ILC2 and ILC3 subsets will serve as valuable resources for future analyses of ILC function and are available at http://skin.science.
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