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Status |
Public on Feb 26, 2018 |
Title |
Id2-deficient NK cells acquire a naïve-like fate (Affymetrix data set) |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
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.
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Overall design |
CD19-Ter119-CD122+NK1.1+CD27+CD11b- natural killer cells were sorted from the bone marrow of 3 Rag1-/-Id2f/f and 3 Rag1-/- GzmbCre Id2f/f mice (littermates) and RNA was extracted for analysis by Affymetrix microarray.
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Contributor(s) |
Zook EC, Li ZY, Xu Y, de Pooter RF, Verykokakis M, Beaulieu A, Lasorella A, Maienschein-Cline M, Sun JC, Sigvardsson M |
Citation(s) |
29703840 |
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Submission date |
Jan 19, 2018 |
Last update date |
Jan 22, 2022 |
Contact name |
Barbara L Kee |
Organization name |
The University of Chicago
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Department |
Pathology
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Street address |
924 E57th st
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City |
Chicago |
State/province |
Illinois |
ZIP/Postal code |
60637 |
Country |
USA |
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Platforms (1) |
GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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Samples (6)
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This SubSeries is part of SuperSeries: |
GSE109518 |
Id2-deficient NK cells acquire a naïve-like fate |
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Relations |
BioProject |
PRJNA430928 |