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Differential requirement for Nfil3 during NK cell development

ABSTRACT: Nfil3 has multiple functions during conventional NK cell and thymic NK cell development. Nfil3 controls NK cell development from the earliest committed NK cell progenitor stage. Nfil3-/- prepro NK cells retained T-cell potential due to the failure to repress T cell specific genes. At later stages of NK cell development, Nfil3 regulates the formation of mature NK cells by promoting directly or indirectly the expression of transcription factor Eomes. We also demonstrate that Nfil3 is important for thymic NK cell development whereas Trail+ immature NK cells generated in the bone marrow of neonates and in the adult liver develop independent of Nfil3 function. We used microarrays to analyse the changes in gene expression due to the presence or absence of Nfil3, both in prepro NK cells and ALP cells (all lymphoid progenitors)

ORGANISM(S): Mus musculus

PROVIDER: GSE45955 | GEO | 2013/10/08

SECONDARY ACCESSION(S): PRJNA196725

REPOSITORIES: GEO

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Differential requirement for Nfil3 during NK cell development

Project description:Nfil3 has multiple functions during conventional NK cell and thymic NK cell development. Nfil3 controls NK cell development from the earliest committed NK cell progenitor stage. Nfil3-/- prepro NK cells retained T-cell potential due to the failure to repress T cell specific genes. At later stages of NK cell development, Nfil3 regulates the formation of mature NK cells by promoting directly or indirectly the expression of transcription factor Eomes. We also demonstrate that Nfil3 is important for thymic NK cell development whereas Trail+ immature NK cells generated in the bone marrow of neonates and in the adult liver develop independent of Nfil3 function. We used microarrays to analyse the changes in gene expression due to the presence or absence of Nfil3, both in prepro NK cells and ALP cells (all lymphoid progenitors) Samples were obtained on two experimentation dates. Replicate 1 was processed in April 2012, replicate 2 was processed in May 2012.

2013-10-08 | E-GEOD-45955 | biostudies-arrayexpress

Differential requirement for Nfil3 during NK cell development

Project description:Natural killer (NK) cells can be grouped into distinct subsets that are localized to different organs and exhibit different capacity to secrete cytokines and mediate cytotoxicity. Despite these hallmarks that reflect tissue-specific specialization in NK cells, little is known about the factors that control the development of these distinct subsets. The basic leucine zipper transcription factor nuclear factor interleukin 3 (Nfil3; E4bp4) is essential for bone marrow-derived NK cell development but it is not clear whether Nfil3 is equally important for all NK cell subsets nor how it induces NK lineage commitment. Here we show that Nfil3 is required for the formation of Eomesodermin (Eomes)-expressing NK cells, including conventional medullary and thymic NK cells, whereas TRAIL+ Eomes- NK cells develop independent of Nfil3. Loss of Nfil3 during the development of bone marrow-derived NK cells resulted in reduced expression of Eomes and, conversely, restoration of Eomes expression in Nfil3-/- progenitors rescued NK cell development and maturation. Collectively, these findings demonstrate that Nfil3 drives the formation of mature NK cell by inducing Eomes expression and reveal the differential requirements of NK cell subsets for Nfil3. RNA-sequencing of natural killer (NK) cell subsets

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Differential requirement for Nfil3 during NK cell development

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The basic leucine zipper transcription factor NFIL3 directs the development of a common innate lymphoid cell precursor

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.

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Tissue-Resident Natural Killer (NK) Cells Are Cell Lineages Distinct From Thymic and Conventional Splenic NK Cells (part 2)

Project description:Natural killer (NK) cells belong to the innate immune system where they can control virus infections and developing tumors by cytotoxicity and production of inflammatory cytokines. Most studies of mouse NK cells, however, have focused on conventional NK (cNK) cells found in the spleen. Recently, we described two populations of NK cells within the liver, tissue-resident NK (trNK) cells and those resembling splenic cNK cells. However, the lineage relationship of trNK to cNK cells was unclear because trNK cells display a phenotype associated with immature, developing cNK cells. Moreover, liver trNK cells could be related to thymic NK cells or alternatively, a lineage distinct from both cNK and thymic NK cells. Herein we used detailed transcriptomic, flow cytometric, and functional analysis of mice deficient in several transcription factors to determine that liver trNK cells form a distinct lineage from cNK and thymic NK cells, especially because they do not require NFIL3 (E4BP4), the previously described NK cellspecification factor. Analysis of other tissues indicate the presence of trNK cells in skin and uterus with different transcription factor requirements. Thus, there are at least four distinct lineages of NK cells: cNK, thymic, liver (and skin) trNK, and uterine trNK cells. Liver DX5-CD49+, liver DX5+CD49-, spleen DX5+ CD49- populations of NK cells were sorted with FACS pooling cells from individual mice to end up with ~100k cells for each samples. mRNA was derived from lysates using Invitrogen oligo-dT beads

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Mus musculus

Project description:Differential requirement for Nfil3 during NK cell development

| PRJNA196725 | ENA

Mus musculus

Project description:Differential requirement for Nfil3 during NK cell development

| PRJNA246298 | ENA

Tissue-Resident Natural Killer (NK) Cells Are Cell Lineages Distinct From Thymic and Conventional Splenic NK Cells (part 2)

2014-04-26 | GSE52045 | GEO