Id2-deficient NK cells acquire a naïve-like fate (Affymetrix data set)
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PROVIDER: PRJNA430928 | ENA |
REPOSITORIES: ENA
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Project description:All innate lymphoid cells (ILC) constitutively express and require the small helix-loop-helix protein ID2 but the functions of ID2 are not well understood in these cells. Here we show that natural killer (NK) cells, the prototypic ILC, can develop in the absence of ID2 but lose their innate properties and remain as CD27+CD11b- cells that fail to mature into cytotoxic effectors. We show that ID2 broadly limited chromatin accessibility at E protein binding sites near T lymphocyte-associated genes including multiple chemokine receptors, cytokine receptors, and signaling molecules. Moreover, ID2 prevented the conversion of CD27+CD11b- NK cells from a CD8 memory precursor-like chromatin accessibility state toward a naïve-like chromatin accessibility state, and altered their functional capacity. Finally, we demonstrate that increased expression of the naïve T cell-associated helix-loop-helix protein ID3 was required for development of ID2-deficient NK cells, indicating that completely unfettered E protein function is incompatible with NK cell development. These data solidify the roles of ID2 and ID3 as mediators of effector and naïve gene programs, respectively, and revealed a critical role for ID2 in promoting a chromatin state and transcriptional program in CD27+CD11b- NK cells that supports the innate properties of these cells and their ability to undergo cytotoxic effector differentiation.
2018-02-26 | GSE109456 | GEO
Project description:Id2-deficient NK cells acquire a naïve-like fate
| PRJNA431284 | ENA
Project description:All innate lymphoid cells (ILC) constitutively express and require the small helix-loop-helix protein ID2 but the functions of ID2 are not well understood in these cells. Here we show that natural killer (NK) cells, the prototypic ILC, can develop in the absence of ID2 but lose their innate properties and remain as CD27+CD11b- cells that fail to mature into cytotoxic effectors. We show that ID2 broadly limited chromatin accessibility at E protein binding sites near T lymphocyte-associated genes including multiple chemokine receptors, cytokine receptors, and signaling molecules. Moreover, ID2 prevented the conversion of CD27+CD11b- NK cells from a CD8 memory precursor-like chromatin accessibility state toward a naïve-like chromatin accessibility state, and altered their functional capacity. Finally, we demonstrate that increased expression of the naïve T cell-associated helix-loop-helix protein ID3 was required for development of ID2-deficient NK cells, indicating that completely unfettered E protein function is incompatible with NK cell development. These data solidify the roles of ID2 and ID3 as mediators of effector and naïve gene programs, respectively, and revealed a critical role for ID2 in promoting a chromatin state and transcriptional program in CD27+CD11b- NK cells that supports the innate properties of these cells and their ability to undergo cytotoxic effector differentiation.
2018-02-26 | GSE109517 | GEO
Project description:Id2-deficient NK cells acquire a naïve-like fate (ATAC-seq data set)
| PRJNA431289 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-02-26 | GSE109518 | GEO
Project description:Expression data from Id2-GFP- CDPs, Id2-GFP+ CDPs, Id2-GFP- pre-CD8, and Id2-GFP+ pre-CD8.
| PRJNA509888 | ENA
Project description:To understand molecular mechanisms by which reducing Id2 rescues impaired erythropoiesis and hematopoietic progenitor cell development in Gfi-1-/- mice, we compared gene expression in Gfi-1-/-;Id2+/- and Gfi-1-/- BMC using Affymetrix microarray.
2014-07-12 | GSE59360 | GEO
Project description:The inhibitor of DNA binding 2 (Id2) is essential for NK cell development with its canonical role in this pathway being to antagonize E-proteins, silencing E-box gene expression and subsequent commitment to the T and B cell lineages. However, how E-box genes prevent NK cell development and homeostasis remains enigmatic. Here we identify a key role for Id2 in regulating the threshold for IL-15 receptor signaling and homeostasis of NK cells by repressing multiple E-protein target genes including Socs3. Deletion of Id2 in mature NK cells was incompatible with their homeostasis due to impaired IL-15 receptor signaling. Id2-null NK cells displayed impaired IL-15 mediated JAK1/STAT5 phosphorylation, compromised metabolic function and enhanced apoptosis. Remarkably, Id2-null NK cell homeostasis could be fully rescued in vivo by IL-15 receptor stimulation and partially rescued by genetic ablation of Socs3. During normal NK cell maturation we observed an inverse correlation between the expression levels of E-protein target genes and Id2. These results shift the current paradigm on the role of Id2, indicating that it is not only required to antagonize E-proteins during NK cell commitment, but constantly required to titrate E-protein activity to regulate NK cell fitness and responsiveness to IL-15.
2016-02-01 | GSE76466 | GEO
Project description:To understand molecular mechanisms by which reducing Id2 rescues impaired erythropoiesis and hematopoietic progenitor cell development in Gfi-1-/- mice, we compared gene expression in Gfi-1-/-;Id2+/- and Gfi-1-/- BMC using Affymetrix microarray. Total RNA samples from four individual Gfi-1-/- or Gfi-1-/-;Id2+/- mice were arrayed using the GeneChip Mouse Gene 1.0 ST Array (Affymetrix, Santa Clara, CA).
2014-07-12 | E-GEOD-59360 | biostudies-arrayexpress
Project description:During an immune response, CD8 T cells fall along a gradient of memory potential, but the regulators of these fate decsisions are not well understood. We utlized Id3-GFP and Id2-YFP reporter mice to elucidate the role of Id3 and Id2 during early CD8 T cell differentiation by gene expression. Id3-GFP hi Id2-YFP int or Id3-GFP lo Id2-YFP hi OT-I cells were sorted into trizol at day 6 of VSV-OVA infection and analyzed by microarray
2011-10-06 | E-GEOD-32675 | biostudies-arrayexpress